Understanding a protein fold: The physics, chemistry, and biology of α-helical coiled coils
Open accessAbstract
Protein science is being transformed by powerful computational methods for structure prediction and design: AlphaFold2 can predict many natural protein structures from sequence, and other AI methods are enabling the de novo design of new structures.This raises a question: how much do we understand the underlying sequence-to-structure/function relationships being captured by these methods?This perspective presents our current understanding of one class of protein assembly, the α-helical coiled coils.At first sight, these are straightforward: sequence repeats of hydrophobic (h) and polar (p) residues, (hpphppp) n , direct the folding and assembly of amphipathic α helices into bundles.However, many different bundles are possible: they can have two or more helices (different oligomers); the helices can have parallel, antiparallel, or mixed arrangements (different topologies); and the helical sequences can be the same (homomers) or different (heteromers).Thus, sequence-to-structure relationships must be present within the hpphppp repeats to distinguish these states.I discuss the current understanding of this problem at three levels: first, physics gives a parametric framework to generate the many possible coiled-coil backbone structures.Second, chemistry provides a means to explore and deliver sequence-to-structure relationships.Third, biology shows how coiled coils are adapted and functionalized in nature, inspiring applications of coiled coils in synthetic biology.I argue that the chemistry is largely understood; the physics is partly solved, though the considerable challenge of predicting even relative stabilities of different coiled-coil states remains; but there is much more to explore in the biology and synthetic biology of coiled coils.
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The free energy landscape of coiled coils is complex, consisting of multiple local, energetically close minima.
“The free energy landscape of coiled coils is complex, consisting of multiple local, energetically close minima.32,33”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [32]
The “Current rules and challenges in coiled-coil design” section describes a complex free-energy landscape with multiple states close in energy, using CC-Hex as an example. “A note of caution” likewise says multiple states may be accessible for the short, low-to-medium-complexity de novo coiled coils discussed there. These passages support the central idea, but not its unqualified extension to coiled coils generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAchieving quantitative predictions of coiled-coil stability by calculating the free energy of oligomerization has been deemed one of the outstanding challenges in coiled coil research.
“For these reasons, achieving quantitative predictions of coiled-coil stability by calculating the free energy of oligomerization has been deemed one of the outstanding challenges in coiled coil research.32”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [32]
Computational design of multistate coiled-coil assemblies is challenging because it requires accurate estimates of the free energy differences between multiple alternative coiled-coil conformations.
“However, the computational design of multistate coiled-coil protein assemblies is challenging, as it requires accurate estimates of the free energy differences between multiple alternative coiled-coil conformations.”
From Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints (2025) · cites this paper as [32]
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“…the apparent simplicity of the leucine zippers belies an underlying complexity, which includes many proteins in humans, the speci fi cation of homo-and hetero-oligomers between these, and differing levels of expression, which combine to give exquisite control over transcription (137, 142, 225, 226).”
High thermodynamic stability of parametrically designed helical bundles
Huang, P.-S., Oberdorfer, G., Xu, C., Pei, X. Y., Nannenga, B. L., Rogers, J. M., DiMaio, F., Gonen, T., Luisi, B., & Baker, D. (2014) · Science · doi:10.1126/science.1257481 · Cited by 277 · cited 3× · see citing works
“Some allow coiled-coil backbones to be built quickly and accurately (28, 31), and others allow full atomistic modeling of coiled coils including side chains (29, 33, 35, 36).”
Heptad breaks in α-helical coiled coils: Stutters and stammers
Brown, J. H., Cohen, C., & Parry, D. A. D. (1996) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(199610)26:2 · Cited by 268 · see citing works
A Buried Polar Interaction Imparts Structural Uniqueness in a Designed Heterodimeric Coiled Coil
Lumb, K. J., & Kim, P. S. (1995) · Biochemistry · doi:10.1021/bi00027a013 · Cited by 266 · see citing works
Fletcher, J. M., Boyle, A. L., Bruning, M., Bartlett, G. J., Vincent, T. L., Zaccai, N. R., Armstrong, C. T., Bromley, E. H. C., Booth, P. J., Brady, R. L., et al. (2012) · ACS Synthetic Biology · doi:10.1021/sb300028q · Cited by 262 · cited 7× · see citing works
“Nonetheless, these systems are being put to good use in a variety of applications, including the following: driving membrane fusion (127, 128); directing the patterned aggregation of bacterial and human cells (129); developing peptide origami by Jerala (65, 80, 130); (89).”
InfluentialSelf-citationDe novo protein design, a retrospective
Korendovych, I. V., & DeGrado, W. F. (2020) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583519000131 · Cited by 249 · see citing works
Strelkov, S. V., & Burkhard, P. (2002) · Journal of Structural Biology · doi:10.1006/jsbi.2002.4454 · Cited by 246 · see citing works
Probing Designability via a Generalized Model of Helical Bundle Geometry
Grigoryan, G., & DeGrado, W. F. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.08.058 · Cited by 232 · cited 4× · see citing works
“Thus, the coiled coil is inherently parametric, which makes it physics, predictable, modelable and, as, we will see, ultimately designable (28).”
InfluentialLiu, J., Zheng, Q., Deng, Y., Cheng, C.-S., Kallenbach, N. R., & Lu, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604871103 · Cited by 227 · cited 2× · see citing works
“From that, rational and computational peptide/protein design and engineering has delivered many examples of these, Figures 4 and 5, A and B (33, 34, 40, 100, 138, 144).”
Designing Heterodimeric Two-stranded α-Helical Coiled-coils
Litowski, J., & Hodges, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204257200 · Cited by 221 · see citing works
Tandem repeats in proteins: From sequence to structure
Kajava, A. V. (2011) · Journal of Structural Biology · doi:10.1016/j.jsb.2011.08.009 · Cited by 221 · cited 1× · see citing works
“I have not touched on this in my perspective, but there are excellent reviews from these groups (110, 111, 285 – 287).”
Recent advances in de novo protein design: Principles, methods, and applications
Pan, X., & Kortemme, T. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100558 · Cited by 221 · cited 1× · see citing works
“While de novo protein design has been active for ≈ 40 years, the fi eld is now advancing rapidly and booming (51, 70, 110 – 112).”
Thompson, K. E., Bashor, C. J., Lim, W. A., & Keating, A. E. (2012) · ACS Synthetic Biology · doi:10.1021/sb200015u · Cited by 218 · cited 3× · see citing works
“Exploring other sequence repeats and mixing and matching those available to increase sequence complexity may help address this issue; indeed, others like Mason, Keating, and Jerala are showing the way here (93, 124, 163).”
Bromley, E. H. C., Channon, K., Moutevelis, E., & Woolfson, D. N. (2008) · ACS Chemical Biology · doi:10.1021/cb700249v · Cited by 217 · cited 1× · see citing works
“In turn, this would allow the modules to be used reliably in synthetic biology to construct more complex and functional protein-like objects (114, 115).”
Self-citationBuried polar residues and structural specificity in the GCN4 leucine zipper
Gonzalez, L. C., Woolfson, D. N., & Alber, T. (1996) · Nature Structural Biology · doi:10.1038/nsb1296-1011 · Cited by 216 · cited 2× · see citing works
“A prime example of this is the conservation of an Asn residue at a central a site in the wider family of leucine-zipper transcription factors (86).”
Self-citationPredicting oligomerization states of coiled coils
Woolfson, D. N., & Alber, T. (1995) · Protein Science · doi:10.1002/pro.5560040818 · Cited by 214 · cited 9× · see citing works
“Nevertheless, since their discovery, Harbury ’ s basic sequence-to-structure relationships have been con fi rmed by analyses of many natural coiled-coil sequences and structures (37, 50, 75) and through quantitative biophysical studies (78, 79).”
InfluentialSelf-citationA Periodic Table of Coiled-Coil Protein Structures
Moutevelis, E., & Woolfson, D. N. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.11.028 · Cited by 204 · see citing works
Self-citationRotary substates of mitochondrial ATP synthase reveal the basis of flexible F 1 -F o coupling
Murphy, B. J., Klusch, N., Langer, J. D., et al. (2019) · Science · doi:10.1126/science.aaw9128 · Cited by 204 · cited 2× · see citing works
“I have already mentioned the α HB structures of E. coli Wza (244) and the F 1 F 0 ATP synthase (104), Figure 5, E and G .”
Burley, S. K., Bhikadiya, C., Bi, C., Bittrich, S., Chen, L., Crichlow, G. V., Duarte, J. M., Dutta, S., Fayazi, M., Feng, Z., et al. (2021) · Protein Science · doi:10.1002/pro.4213 · Cited by 203 · see citing works
The Structure of Synthetic Polypeptides
Pauling, L. C., & Corey, R. B. (1951) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.37.5.241 · Cited by 202 · cited 1× · see citing works
“However, Pauling et al. considered other repeats in α -helical conformations, speci fi cally, those with 11, 15, and 18 residues (25, 54).”
Coiled Coils – A Model System for the 21st Century
Lupas, A. N., & Baßler, J. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.10.007 · Cited by 199 · cited 2× · see citing works
“Coiled-coil function has been surveyed in good reviews over the years (8 – 11 , 13 )”
Refinement of the influenza virus hemagglutinin by simulated annealing
Weis, W. I., Brünger, A. T., Skehel, J. J., & Wiley, D. C. (1990) · Journal of Molecular Biology · doi:10.1016/0022-2836(90)90234-d · Cited by 198 · see citing works
A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering
Reinke, A. W., Grant, R. A., & Keating, A. E. (2010) · Journal of the American Chemical Society · doi:10.1021/ja907617a · Cited by 197 · cited 1× · see citing works
“…systems, including the following: the aforementioned designs from O ’ Shea and Kim, “ peptide Velcro ” (116), and from Litowski and Hodges, “ E/K coil ” peptides (117, 118); Keating ’ s “ SYN-ZIP ” designs (123, 124); and the sets of coiled-coil hetero-dimers from Jerala (91, 125) and Mason (93).”
Structure of cytoplasmic ring of nuclear pore complex by integrative cryo-EM and AlphaFold
Fontana, P., Dong, Y., Pi, X., Tong, A. B., Hecksel, C. W., Wang, L., Fu, T.-M., Bustamante, C., & Wu, H. (2022) · Science · doi:10.1126/science.abm9326 · Cited by 195 · cited 2× · see citing works
“…important biophysical properties such as coiled-coil dynamics, exchange, and turnover; moving beyond coiled coils as simple oligomerization domains and spacers and exploring the complexity of coiled-coil architectures in the context of larger and functional biological assemblies (235, 240).”
A de novo peptide hexamer with a mutable channel
Zaccai, N. R., Chi, B., Thomson, A. R., Boyle, A. L., Bartlett, G. J., Bruning, M., Linden, N., Sessions, R. B., Booth, P. J., Brady, R. L., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.692 · Cited by 192 · cited 13× · see citing works
“Indeed, we have observed this for CC-Tet and some α HB systems (89, 100, 109, 144, 145, 181), and others have reported changes in oligomer states when incorporating some of the modules into larger fusion proteins (197, 198).”
InfluentialSelf-citationDeepCoil—a fast and accurate prediction of coiled-coil domains in protein sequences
Ludwiczak, J., Winski, A., Szczepaniak, K., Alva, V., & Dunin-Horkawicz, S. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty1062 · Cited by 184 · cited 1× · see citing works
“These include the following: Lupas ’ s original COILS program (60) (now PCOIL), DeepCoil (61), and MARCOIL (62).”
Monera, O. D., Zhou, N., Kay, C. M., & Hodges, R. S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36502-0 · Cited by 183 · see citing works
Stereochemical Criteria for Polypeptide and Protein Chain Conformations
Ramachandran, G. N., Venkatachalam, C. M., & Krimm, S. (1966) · Biophysical Journal · doi:10.1016/s0006-3495(66)86699-7 · Cited by 183 · cited 1× · see citing works
“As a consequence of steric constraints in polypeptide chains — as later formalized by Ramachandran in his famous plot (26, 27) — the α helix has precisely 3.6 residues per turn (Fig.”
InfluentialDesign of coiled-coil protein-origami cages that self-assemble in vitro and in vivo
Ljubetič, A., Lapenta, F., Gradišar, H., Drobnak, I., Aupič, J., Strmšek, Ž., Lainšček, D., Hafner‐Bratkovič, I., Majerle, A., Krivec, N., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3994 · Cited by 178 · cited 4× · see citing works
“Exploring other sequence repeats and mixing and matching those available to increase sequence complexity may help address this issue; indeed, others like Mason, Keating, and Jerala are showing the way here (93, 124, 163).”
InfluentialModel systems for membrane fusion
Marsden, H. R., Tomatsu, I., & Kros, A. (2010) · Chemical Society Reviews · doi:10.1039/c0cs00115e · Cited by 177 · cited 2× · see citing works
“This principle has been exploited to drive membrane fusion in a variety of synthetic and biological membrane systems by Kros et al. (127, 128).”
An autonomous folding unit mediates the assembly of two-stranded coiled coils
Kammerer, R. A., Schulthess, T., Landwehr, R., Lustig, A., Engel, J., Aebi, U., & Steinmetz, M. O. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13419 · Cited by 174 · cited 1× · see citing works
“Possibilities here include nature ’ s inclusion of nonheptad sequence repeats (55, 56) and so-called trigger sequences for folding (277 – 279).”
Monera, O. D., Kay, C. M., & Hodges, R. S. (1994) · Biochemistry · doi:10.1021/bi00179a010 · Cited by 170 · see citing works
Crystal structure of a naturally occurring parallel right-handed coiled coil tetramer.
Stetefeld, J., Kammerer, R. A., Jenny, M., Schulthess, T., Landwehr, R., & Engel, J. (2000) · Nature Structural Biology · doi:10.1038/79006 · Cited by 170 · cited 1× · see citing works
“However, given the hyperthermal stability possible with even relatively short coiled coils (33, 34, 85), the disruption of perfect hydrophobic repeats is almost certainly essential for protein dynamics and turnover in natural coiled coils.”
Amino-Acid Sequence of Rabbit Skeletal Tropomyosin and Its Coiled-Coil Structure
Sodek, J., Hodges, R. S., Smillie, L. B., et al. (1972) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.69.12.3800 · Cited by 170 · cited 1× · see citing works
“In 1972, Sodek et al. reported the partial sequence of rabbit tropomyosin (42), which was anticipated to be an extended dimeric coiled coil.”
Selective motor activation in organelle transport along axons
Cason, S. E., & Holzbaur, E. L. F. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00491-w · Cited by 169 · cited 1× · see citing works
“However, as has been known for some time (246, 247), there is a lot more to these coiled-coil proteins than the simple text-book picture portrays.”
Computational design of transmembrane pores
Xu, C., Lu, P., El-Din, T. M. G., Pei, X. Y., Johnson, M. C., Uyeda, A., Bick, M. J., Xu, Q. K., Jiang, D., Bai, H., et al. (2020) · Nature · doi:10.1038/s41586-020-2646-5 · Cited by 169 · cited 2× · see citing works
“Speci fi cally on the latter, the DeGrado and Baker groups have used sequence-to-structure relationships garnered from the α HBs to stabilize pentameric bundles of phospholamban (218) and in the de novo design of ion channels (219), respectively.”
Verardi, R., Shi, L., Traaseth, N. J., Walsh, N., & Veglia, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016535108 · Cited by 168 · cited 2× · see citing works
“Smaller transmembrane barrels include the ion channel phospholamban, which is a pentamer as shown by a combined solution and solid-state NMR structure determined in lipid bilayers, Figure 5 H (272).”
Conway, J. F., & Parry, D. A. D. (1990) · International Journal of Biological Macromolecules · doi:10.1016/0141-8130(90)90023-4 · Cited by 167 · see citing works
Thomas, F., Boyle, A. L., Burton, A. J., & Woolfson, D. N. (2013) · Journal of the American Chemical Society · doi:10.1021/ja312310g · Cited by 164 · cited 8× · see citing works
“…peptide synthesis or as fusions to proteins of interest via gene synthesis and recombinant expression; (ii) they can be adapted to render a range of association constants from μ M to pM (92, 183); and (iii) in several cases, multiple orthogonal pairs have been engineered (91 – 94, 124, 182).”
InfluentialSelf-citationCoiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence
McNamara, C. W., Zinkernagel, A. S., Machebœuf, P., Cunningham, M. W., Nizet, V., & Ghosh, P. (2008) · Science · doi:10.1126/science.1154470 · Cited by 163 · cited 1× · see citing works
“While on altered and dynamic packing arrangements in natural coiled coils, I should mention Ghosh ’ s work on the surface-associated M proteins of Streptococcus pyogenes (Strep A) (274).”
CC+: a relational database of coiled-coil structures
Testa, O. D., Moutevelis, E., & Woolfson, D. N. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn675 · Cited by 158 · cited 8× · see citing works
“Nevertheless, since their discovery, Harbury ’ s basic sequence-to-structure relationships have been con fi rmed by analyses of many natural coiled-coil sequences and structures (37, 50, 75) and through quantitative biophysical studies (78, 79).”
InfluentialSelf-citationDe novo protein design: how do we expand into the universe of possible protein structures?
Woolfson, D. N., Bartlett, G. J., Burton, A. J., Heal, J. W., Niitsu, A., Thomson, A. R., & Wood, C. W. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.05.009 · Cited by 155 · cited 2× · see citing works
“As discussed in previous sections, α HBs have expanded our understanding and our reach into coiled-coil structural space, and they have inspired new protein designs (13, 140, 245).”
Self-citationModular Design of Self-Assembling Peptide-Based Nanotubes
Burgess, N. C., Sharp, T. H., Thomas, F., Wood, C. W., Thomson, A. R., Zaccai, N. R., Brady, R. L., Serpell, L. C., & Woolfson, D. N. (2015) · Journal of the American Chemical Society · doi:10.1021/jacs.5b03973 · Cited by 154 · cited 1× · see citing works
“Our adaptations of the α HBs have included the following: assembling peptide-based fi bers and nanotubes (176, 177), following the approach of Conticello (178); installing a Cys-His-Glu catalytic triad in the channel of CC-Hept to effect ester hydrolysis; developing receptors for reporters dyes and…”
Self-citationDesigned heterodimerizing leucine zippers with a ranger of pIs and stabilities up to 10−15 M
Moll, J. R., Ruvinov, S., Pastan, I., & Vinson, C. (2001) · Protein Science · doi:10.1110/ps.39401 · Cited by 153 · cited 3× · see citing works
“…de novo coiled-coil modules have been CC-Di-AB (92) and related heterodimeric systems, such as Hodges ’ E/K peptides (117, 118), Keating ’ s SYNZIP systems (124), and others from Jerala (91, 94), Mason (93, 182), O ’ Shea JBC REVIEWS: Understanding α -helical coiled coils (116), and Vinson (183).”
A Reduced SNARE Model for Membrane Fusion
Marsden, H. R., Elbers, N. A., Bomans, P. H. H., Sommerdijk, N. A. J. M., & Kros, A. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200804493 · Cited by 152 · cited 2× · see citing works
“This principle has been exploited to drive membrane fusion in a variety of synthetic and biological membrane systems by Kros et al. (127, 128).”
Repacking protein cores with backbone freedom: structure prediction for coiled coils.
Harbury, P. B., Tidor, B., & Kim, P. S. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8408 · Cited by 149 · see citing works
Mason, J. M., Schmitz, M. A., Müller, K. M., & Arndt, K. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509880103 · Cited by 149 · cited 1× · see citing works
“PDB, Protein Data Bank. as “ peptide-PAINT ” or “ live-PAINT ” for high-resolution light microscopy (131, 132); and targeting natural coiled coils in vitro and in cells (133 – 137).”
Coiled-Coil Design: Updated and Upgraded
Woolfson, D. N. (2017) · Subcellular Biochemistry · doi:10.1007/978-3-319-49674-0_2 · Cited by 149 · cited 3× · see citing works
“Moreover, they have been used widely as rules for protein design by many groups to deliver many de novo – designed coiled-coil peptides and proteins (12, 14, 51, 70, 80), which are described in more detail below.”
Self-citationVisualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based Kinase Reporter
Zhang, Q., Huang, H., Zhang, L., Wu, R. S., Chung, C.-I., Zhang, S., Torra, J., Schepis, A., Coughlin, S. R., Kornberg, T. B., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2017.12.008 · Cited by 149 · cited 1× · see citing works
“…aromatic cores that might be suitable for electron transfer (82, 83); to direct the assembly of reversible protein condensates in living cells (213, 214); to encapsulate carbon nanotubes with these water-soluble peptides (215); to explore valency effects in natural protein – protein interactions,…”
A computationally directed screen identifying interacting coiled coils from Saccharomyces cerevisiae
Newman, J. R., Wolf, E., & Kim, P. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.24.13203 · Cited by 148 · cited 1× · see citing works
“These coupled with genome sequencing have led to coiled-coil predictions for whole genomes (228 – 233).”
Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm
Lee, M. J., Mantell, J., Hodgson, L. R., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2535 · Cited by 148 · cited 1× · see citing works
“…of these in cell delivery and vaccine development (168, 169); the construction of arti fi cial transcription factors (119, 170) and cytoscaffolds (171) that assemble and function in bacterial cells; the directed assembly of large DNA origamis (172); the presentation of functioning hotspot…”
Self-citationA Designed Heterotrimeric Coiled Coil
Nautiyal, S., Woolfson, D. N., King, D., & Alber, T. (1995) · Biochemistry · doi:10.1021/bi00037a001 · Cited by 143 · cited 1× · see citing works
“Previously, with Alber, we had used the idea of electrostatic hetero-speci fi cation in computational design to make a hetero-trimer, CC-Tri-ABC (120), a structure for which was later determined by X-ray crystallography, Figure 4 (121).”
Self-citationHistorical review: Another 50th anniversary – new periodicities in coiled coils
Gruber, M. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.10.008 · Cited by 141 · cited 1× · see citing works
“Crick ’ s formalism has been con fi rmed by numerous experiments and analyses over the past 4 to 5 decades (20, 41), as illustrated by the following.”
A brief history of de novo protein design: minimal, rational, and computational.
Woolfson, D. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167160 · Cited by 139 · cited 5× · see citing works
“The history and achievements of this sub fi eld are well documented (12, 14, 51, 70, 80), so I will not repeat it here.”
InfluentialSelf-citationRose, A., Schraegle, S. J., Stahlberg, E. A., & Meier, I. (2005) · BMC Evolutionary Biology · doi:10.1186/1471-2148-5-66 · Cited by 135 · see citing works
A tunable orthogonal coiled-coil interaction toolbox for engineering mammalian cells
Lebar, T., Lainšček, D., Merljak, E., Aupič, J., & Jerala, R. (2020) · Nature Chemical Biology · doi:10.1038/s41589-019-0443-y · Cited by 134 · cited 1× · see citing works
“Exploring other sequence repeats and mixing and matching those available to increase sequence complexity may help address this issue; indeed, others like Mason, Keating, and Jerala are showing the way here (93, 124, 163).”
Packing of apolar side chains enables accurate design of highly stable membrane proteins
Mravic, M., Thomaston, J. L., Tucker, M. R., Solomon, P. E., Liu, L., & DeGrado, W. F. (2019) · Science · doi:10.1126/science.aav7541 · Cited by 133 · cited 3× · see citing works
“Speci fi cally on the latter, the DeGrado and Baker groups have used sequence-to-structure relationships garnered from the α HBs to stabilize pentameric bundles of phospholamban (218) and in the de novo design of ion channels (219), respectively.”
The design of antiparallel coiled coils
Oakley, M. G. (2001) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(00)00232-3 · Cited by 131 · see citing works
Synthetic protein condensates for cellular and metabolic engineering
Qian, Z., Huang, S.-C., & Xia, X. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01203-3 · Cited by 131 · see citing works
Spy&Go purification of SpyTag-proteins using pseudo-SpyCatcher to access an oligomerization toolbox
Anuar, I. N. A. K., Banerjee, A., Keeble, A. H., Carella, A., Nikov, G. I., & Howarth, M. R. (2019) · Nature Communications · doi:10.1038/s41467-019-09678-w · Cited by 130 · cited 1× · see citing works
“…to explore valency effects in natural protein – protein interactions, e.g. , galectin-glycan binding (216); to develop Spy&Go, augmenting the widely used SpyCatcher system through multi-merization (217); and to facilitate the engineering and de novo design of transmembrane proteins (218, 219).”
Scaffolds, levers, rods and springs: diverse cellular functions of long coiled-coil proteins
Rose, A., & Meier, I. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4039-6 · Cited by 129 · cited 1× · see citing works
“Coiled-coil function has been surveyed in good reviews over the years (8 – 11 , 13 )”
C CB uilder 2.0: Powerful and accessible coiled‐coil modeling
Wood, C. W., & Woolfson, D. N. (2017) · Protein Science · doi:10.1002/pro.3279 · Cited by 129 · see citing works
Self-citationMolecular and environmental determinants of biomolecular condensate formation
Villegas, J. A., Heidenreich, M., & Levy, E. D. (2022) · Nature Chemical Biology · doi:10.1038/s41589-022-01175-4 · Cited by 129 · cited 1× · see citing works
“For introductions to biomolecular condensation and phase separation in nature and synthetic biology, two excellent reviews have been published in a special issue of Nature Chemical Biology (254, 255).”
Constructing ion channels from water-soluble α-helical barrels
Scott, A. J., Niitsu, A., Kratochvil, H. T., Lang, E. J. M., Sengel, J. T., Dawson, W., Mahendran, K. R., Mravic, M., Thomson, A. R., Brady, R. L., et al. (2021) · Nature Chemistry · doi:10.1038/s41557-021-00688-0 · Cited by 125 · cited 2× · see citing works
“Indeed, we have observed this for CC-Tet and some α HB systems (89, 100, 109, 144, 145, 181), and others have reported changes in oligomer states when incorporating some of the modules into larger fusion proteins (197, 198).”
Self-citationA monodisperse transmembrane α-helical peptide barrel
Mahendran, K. R., Niitsu, A., Kong, L., Thomson, A. R., Sessions, R. B., Woolfson, D. N., & Bayley, H. (2016) · Nature Chemistry · doi:10.1038/nchem.2647 · Cited by 123 · cited 1× · see citing works
“Wza has inspired the design of a peptide-based ion channel (271).”
Self-citationDe novo design of orthogonal peptide pairs forming parallel coiled‐coil heterodimers
Gradišar, H., & Jerala, R. (2010) · Journal of Peptide Science · doi:10.1002/psc.1331 · Cited by 122 · cited 7× · see citing works
“Nonetheless, these systems are being put to good use in a variety of applications, including the following: driving membrane fusion (127, 128); directing the patterned aggregation of bacterial and human cells (129); developing peptide origami by Jerala (65, 80, 130); (89).”
InfluentialBurkhard, P., Kammerer, R. A., Steinmetz, M. O., Bourenkov, G. P., & Aebi, U. (2000) · Structure · doi:10.1016/s0969-2126(00)00100-3 · Cited by 121 · cited 1× · see citing works
“Possibilities here include nature ’ s inclusion of nonheptad sequence repeats (55, 56) and so-called trigger sequences for folding (277 – 279).”
Structural Plasticity of Helical Nanotubes Based on Coiled-Coil Assemblies
Egelman, E. H., Xu, C., DiMaio, F., Magnotti, E. L., Modlin, C., Yu, X., Wright, E., Baker, D. A., & Conticello, V. P. (2015) · Structure · doi:10.1016/j.str.2014.12.008 · Cited by 120 · cited 1× · see citing works
“…called these Type III interfaces, which are manifested in large helical barrels such as the 12-helix assembly of TolC (103) and more recent structures of the F 1 F 0 ATP synthase (104); and they are being used in design by Conticello et al. to design fi brous and nanotubular assemblies (105 – 107).”
A distinct 14 residue site triggers coiled‐coil formation in cortexillin I
Steinmetz, M. O., Stock, A., Schulthess, T., Landwehr, R., Lustig, A., Faix, J., Gerisch, G., Aebi, U., & Kammerer, R. A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.7.1883 · Cited by 119 · see citing works
Rational Design of Helical Nanotubes from Self-Assembly of Coiled-Coil Lock Washers
Xu, C., Liu, R., Mehta, A. K., Guerrero-Ferreira, R., Wright, E. R., Dunin-Horkawicz, S., Morris, K. L., Serpell, L. C., Zuo, X., Wall, J. S., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4074529 · Cited by 119 · cited 4× · see citing works
“…of the α HBs have included the following: assembling peptide-based fi bers and nanotubes (176, 177), following the approach of Conticello (178); installing a Cys-His-Glu catalytic triad in the channel of CC-Hept to effect ester hydrolysis; developing receptors for reporters dyes and…”
InfluentialThe Structure and Topology of α-Helical Coiled Coils
Lupas, A. N., Baßler, J., & Dunin-Horkawicz, S. (2017) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-319-49674-0_4 · Cited by 116 · cited 5× · see citing works
“With some tweaks, the main tenets of Crick ’ s model are evident and validated by these structures and analyses (19, 20, 37, 50).”
InfluentialIcosahedral bacteriophage ΦX174 forms a tail for DNA transport during infection
Sun, L., Young, L. N., Zhang, X., Boudko, S. P., Fokine, A., Zbornik, E. A., Roznowski, A. P., Molineux, I. J., Rossmann, M. G., & Fane, B. A. (2013) · Nature · doi:10.1038/nature12816 · Cited by 116 · cited 1× · see citing works
“F , the H protein from the Φ X174 coliphage forms a 10-stranded α - helical tube, which can span the periplasm of the host to deliver its ssDNA genome (4jpp (291)).”
Chaperoning SNARE Folding and Assembly
Zhang, Y., & Hughson, F. M. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-081820-103615 · Cited by 115 · cited 1× · see citing works
“The eukaryotic SNARE and related proteins involved in intracellular vesicular traf fi cking also promote membrane fusion, though through a very different mechanism (267 – 270).”
Acharya, A., Ruvinov, S. B., Gál, J., et al. (2002) · Biochemistry · doi:10.1021/bi020486r · Cited by 112 · cited 1× · see citing works
“Nevertheless, since their discovery, Harbury ’ s basic sequence-to-structure relationships have been con fi rmed by analyses of many natural coiled-coil sequences and structures (37, 50, 75) and through quantitative biophysical studies (78, 79).”
Predicting specificity in bZIP coiled-coil protein interactions
Fong, J. H., Keating, A. E., & Singh, M. (2004) · Genome biology · doi:10.1186/gb-2004-5-2-r11 · Cited by 111 · cited 6× · see citing works
“…the apparent simplicity of the leucine zippers belies an underlying complexity, which includes many proteins in humans, the speci fi cation of homo-and hetero-oligomers between these, and differing levels of expression, which combine to give exquisite control over transcription (137, 142, 225, 226).”
InfluentialThe Alacoil: A very tight, antiparallel coiled‐coil of helices
Gernert, K. M., Surles, M. C., LaBean, T. H., Richardson, J. S., & Richardson, D. C. (1995) · Protein Science · doi:10.1002/pro.5560041102 · Cited by 111 · cited 2× · see citing works
“…antiparallel coiled-coil tetramers: the use of a = d = Leu or better a = Leu d = Ile cores; an obligate Ala at e , similar to so-called Alacoils (151); a preference for Gln at g ; and the use of charge complementarity at b & c as a fi nal guide to helix-helix speci fi cation and orientation, and…”
Wood, C. W., Bruning, M., Ibarra, A. Á., Bartlett, G. J., Thomson, A. R., Sessions, R. B., Brady, R. L., & Woolfson, D. N. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu502 · Cited by 110 · cited 5× · see citing works
“All images were made in PyMol (pymol.org) using the PDB codes given or from models generated in CCBuilder/ISAMBARD (29, 35, 36).”
InfluentialSelf-citationExtended knobs-into-holes packing in classical and complex coiled-coil assemblies☆
Walshaw, J., & Woolfson, D. N. (2003) · Journal of Structural Biology · doi:10.1016/j.jsb.2003.10.014 · Cited by 104 · cited 4× · see citing works
“The idea that residues at e and g sites progressively become involved in coiled-coil interfaces with increasing oligomeric state was fi rst formalized by Wal-shaw (96, 97), though Dunker and Zaleske considered the more general problem earlier (98), as did DeGrado et al. (99) at about the same time as Walshaw.”
InfluentialSelf-citationSquaring the Circle in Peptide Assembly: From Fibers to Discrete Nanostructures by de Novo Design
Boyle, A. L., Bromley, E. H. C., Bartlett, G. J., Sessions, R. B., Sharp, T. H., Williams, C. L., Curmi, P. M. G., Forde, N. R., Linke, H., & Woolfson, D. N. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3053943 · Cited by 103 · cited 1× · see citing works
“In turn, this would allow the modules to be used reliably in synthetic biology to construct more complex and functional protein-like objects (114, 115).”
Self-citationLOGICOIL—multi-state prediction of coiled-coil oligomeric state
Vincent, T. L., Green, P. J., & Woolfson, D. N. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts648 · Cited by 103 · cited 1× · see citing works
“However, the following are currently available: LOGICOIL (63) (http://coiledcoils.chm.bris.ac.uk/LOGICOIL/) and Multicoil2 (64) (http://cb.csail.mit.edu/cb/multicoil2/cgi-bin/ multicoil2.cgi).”
Self-citationVimentin Coil 1A—A Molecular Switch Involved in the Initiation of Filament Elongation
Meier, M., Padilla‐Meier, G. P., Herrmann, H. O., Wedig, T., Hergt, M., Patel, T. R., Stetefeld, J., Aebi, U., & Burkhard, P. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.04.067 · Cited by 101 · cited 1× · see citing works
“Despite the apparent rigidity and stability of these IF coiled-coil assemblies, regions of the structure have been shown to be more labile, which may impact on folding, assembly, function, and misfunction (252, 253).”
Acharya, A., Rishi, V., & Vinson, C. (2006) · Biochemistry · doi:10.1021/bi060822u · Cited by 98 · cited 1× · see citing works
“Nevertheless, since their discovery, Harbury ’ s basic sequence-to-structure relationships have been con fi rmed by analyses of many natural coiled-coil sequences and structures (37, 50, 75) and through quantitative biophysical studies (78, 79).”
The evolution and structure prediction of coiled coils across all genomes.
Rackham, O. J. L., Madera, M., Armstrong, C. T., Vincent, T. L., Woolfson, D. N., & Gough, J. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.08.032 · Cited by 97 · cited 1× · see citing works
“Estimates across all genomes suggest ≈ 0.5 to 6.5% of protein sequences contain coiled-coil regions (232).”
InfluentialSelf-citationFlexible, symmetry-directed approach to assembling protein cages
Sciore, A., Su, M., Koldewey, P., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1606013113 · Cited by 96 · cited 1× · see citing works
“…too (see below); to construct arti fi cial cages by appending CC-Tri, CC-Tet, or CC-Pent to natural proteins with complementary symmetries (199 – 202); to form de fi ned oligomers of photosynthetic reaction centers in membranes (203); to display multiple sugar moieties (204), small-molecule –…”
A coiled-coil masking domain for selective activation of therapeutic antibodies
Trang, V. H., Zhang, X., Yumul, R., Zeng, W., Stone, I. J., Wo, S., Dominguez, M. M. C., Cochran, J. H., Simmons, J. K., Ryan, M. C., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0135-x · Cited by 93 · cited 1× · see citing works
“…factors in Escherichia coli (193); designing molecular switches (beacons) for detecting natural proteins (194); masking therapeutic antibodies that can be activated by proteolysis of the coiled coils (195); and appending them to natural bacterial proteins to direct fi ber formation (196).”
Trigg, J., Gutwin, K., Keating, A. E., & Berger, B. (2011) · PLoS One · doi:10.1371/journal.pone.0023519 · Cited by 91 · cited 1× · see citing works
“However, the following are currently available: LOGICOIL (63) (http://coiledcoils.chm.bris.ac.uk/LOGICOIL/) and Multicoil2 (64) (http://cb.csail.mit.edu/cb/multicoil2/cgi-bin/ multicoil2.cgi).”
Guo, L., Bi, W., Wang, X., Xu, W., Yan, R., Zhang, Y., Zhao, K., Li, Y., Zhang, M., Cai, X., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00438-w · Cited by 91 · see citing works
Probing the “Dark Matter” of Protein Fold Space
Taylor, W. R., Chelliah, V., Hollup, S. M., MacDonald, J. T., & Jonassen, I. (2009) · Structure · doi:10.1016/j.str.2009.07.012 · Cited by 87 · cited 1× · see citing works
“Thus, the hexamer and heptamer open up potential “ dark-matter ” protein structures to explore and exploit (139, 140).”
Litowski, J. R., & Hodges, R. S. (2001) · Journal of Peptide Research · doi:10.1034/j.1399-3011.2001.10972.x · Cited by 84 · cited 6× · see citing works
“Many others have developed heterodimeric AB systems, including the following: the aforementioned designs from O ’ Shea and Kim, “ peptide Velcro ” (116), and from Litowski and Hodges, “ E/K coil ” peptides (117, 118); Keating ’ s “ SYN-ZIP ” designs (123, 124); and the sets of coiled-coil hetero-dimers from Jerala (91…”
InfluentialSequence and Structural Duality: Designing Peptides to Adopt Two Stable Conformations
Pandya, M. J., Cerasoli, E., Joseph, A., Stoneman, R. G., Waite, E., & Woolfson, D. N. (2004) · Journal of the American Chemical Society · doi:10.1021/ja045568c · Cited by 83 · cited 1× · see citing works
“As a result, true and robust sequence-to-structure relationships are dif fi cult to decipher (37, 161).”
Self-citationThe Myosin Family of Mechanoenzymes: From Mechanisms to Therapeutic Approaches
Trivedi, D. V., Nag, S., Spudich, A., Ruppel, K. M., & Spudich, J. A. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011520-105234 · Cited by 83 · cited 1× · see citing works
“However, as has been known for some time (246, 247), there is a lot more to these coiled-coil proteins than the simple text-book picture portrays.”
Three-stranded α-fibrous proteins: the heptad repeat and its implications for structure
Conway, J. F., & Parry, D. A. D. (1991) · International Journal of Biological Macromolecules · doi:10.1016/0141-8130(91)90004-e · Cited by 80 · see citing works
The de novo design of α-helical peptides for supramolecular self-assembly
Beesley, J. L., & Woolfson, D. N. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.03.017 · Cited by 79 · cited 1× · see citing works
“This plurality of heterodimeric modules has helped advance synthetic biology, vesicle/proto-cell work, and protein origami, as reviewed elsewhere (15, 16).”
Self-citationPreferred side-chain constellations at antiparallel coiled-coil interfaces
Hadley, E. B., Testa, O. D., Woolfson, D. N., & Gellman, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709068105 · Cited by 79 · see citing works
Self-citationLiquid–liquid phase separation of the Golgi matrix protein GM130
Rebane, A. A., Ziltener, P., LaMonica, L. C., Bauer, A. H., Zheng, H., López‐Montero, I., Pincet, F., Rothman, J. E., & Ernst, A. M. (2019) · FEBS Letters · doi:10.1002/1873-3468.13715 · Cited by 79 · cited 1× · see citing works
“Moving out of the nucleus, the coiled-coil golgi protein GM130 and other members of the golgin family have been shown to undergo LLPS in vitro and when overexpressed in HeLa cells (262, 265).”
A coiled-coil motif that sequesters ions to the hydrophobic core
Hartmann, M. D., Ridderbusch, O., Zeth, K., Albrecht, R., Testa, O. D., Woolfson, D. N., Sauer, G., Dunin-Horkawicz, S., Lupas, A. N., & Alvarez, B. H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907256106 · Cited by 78 · see citing works
Self-citationMiniprotein Design: Past, Present, and Prospects
Baker, E. G., Bartlett, G. J., Goff, K. L. P., & Woolfson, D. N. (2017) · Accounts of Chemical Research · doi:10.1021/acs.accounts.7b00186 · Cited by 77 · cited 1× · see citing works
“Indeed, the ≈ 30-residue leucine-zipper domains are half the size of even the smallest recognized globular proteins and on a par with so-called miniproteins, which are a niche type of protein (72).”
Self-citationNMR solution structure of a highly stable de novo heterodimeric coiled‐coil
Lindhout, D. A., Litowski, J. R., Mercier, P., Hodges, R. S., & Sykes, B. D. (2004) · Biopolymers · doi:10.1002/bip.20150 · Cited by 75 · see citing works
Atomic structure of a tryptophan-zipper pentamer
Liu, J., Wei, Y., Deng, Y., Kallenbach, N. R., & Lu, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405319101 · Cited by 75 · cited 1× · see citing works
“Indeed, although aromatic residues can be introduced into both natural and de novo coiled-coil peptides, they tend to result in unusual structures that go beyond the classical and symmetric dimers, trimers, and tetramers (81 – 84).”
Coiled coil protein origami: from modular design principles towards biotechnological applications.
Lapenta, F., Aupič, J., Strmšek, Ž., & Jerala, R. (2018) · Chemical Society Reviews · doi:10.1039/c7cs00822h · Cited by 74 · cited 2× · see citing works
“Such an article would be redundant because many excellent reviews are already available (8 – 14), as are others covering newer topics such as the applications of natural and designed coiled coils in biotechnology and synthetic biology (15 – 18).”
Cryo-EM structure of the inhibited (10S) form of myosin II
Yang, S., Tiwari, P., Lee, K. H., Satō, O., Ikebe, M., Padrón, R., & Craig, R. W. (2020) · Nature · doi:10.1038/s41586-020-3007-0 · Cited by 74 · see citing works
Design and Characterization of a Homodimeric Antiparallel Coiled Coil
Gurnon, D. G., Whitaker, J. A., & Oakley, M. G. (2003) · Journal of the American Chemical Society · doi:10.1021/ja0357590 · Cited by 73 · see citing works
Yang, Z., Sun, J., Chen, Y., Zhu, P., Zhang, L., Wu, S., Ma, D., Cao, Q., Li, Z., & Xu, T. (2019) · BMC Genetics · doi:10.1186/s12863-019-0743-y · Cited by 73 · see citing works
Supramolecular Metal-Coordination Polymers, Nets, and Frameworks from Synthetic Coiled-Coil Peptides
Tavenor, N. A., Murnin, M. J., & Horne, W. S. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b00651 · Cited by 72 · cited 1× · see citing works
“…and functional proteins (206, 207) on oligo-meric protein scaffolds; in combination with metal coordination, to drive supramolecular assembly (208, 209); to design metalloproteins (210); and to explore the fundamentals of coiled-coil assembly (211), including the incorporation of nonproteinogenic…”
Controlling the Assembly of Coiled–Coil Peptide Nanotubes
Thomas, F., Burgess, N. C., Thomson, A. R., & Woolfson, D. N. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201509304 · Cited by 72 · cited 1× · see citing works
“Our adaptations of the α HBs have included the following: assembling peptide-based fi bers and nanotubes (176, 177), following the approach of Conticello (178); installing a Cys-His-Glu catalytic triad in the channel of CC-Hept to effect ester hydrolysis; developing receptors for reporters dyes and…”
Self-citationMcClain, D. L., Woods, H. L., & Oakley, M. G. (2001) · Journal of the American Chemical Society · doi:10.1021/ja004099l · Cited by 71 · cited 2× · see citing works
“…at e , similar to so-called Alacoils (151); a preference for Gln at g ; and the use of charge complementarity at b & c as a fi nal guide to helix-helix speci fi cation and orientation, and speci fi cally, using oppositely charged residues in the N-and C-terminal halves of these designs (152 – 154).”
Self-Assembly of an α-Helical Peptide into a Crystalline Two-Dimensional Nanoporous Framework
Magnotti, E. L., Hughes, S. A., Dillard, R. S., Wang, S., Hough, L., Karumbamkandathil, A., Lian, T. T., Wall, J. S., Zuo, X., Wright, E., et al. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b06592 · Cited by 71 · see citing works
Tunn, I., Harrington, M. J., & Blank, K. G. (2019) · Biomimetics · doi:10.3390/biomimetics4010025 · Cited by 69 · cited 1× · see citing works
“…displacement in peptide – peptide interactions (189); exploring the mechanics of biomaterials using biomolecular simulations and experiments (190 – 192); engineering hybrid (natural plus designed) arti fi cial transcription factors in Escherichia coli (193); designing molecular switches (beacons)…”
Rose, A., Manikantan, S., Schraegle, S. J., et al. (2004) · PLANT PHYSIOLOGY · doi:10.1104/pp.103.035626 · Cited by 69 · see citing works
Structure of the shutdown state of myosin-2
Scarff, C. A., Carrington, G., Casas-Mao, D. E., Chalovich, J. M., Knight, P. J., Ranson, N. A., & Peckham, M. (2020) · Nature · doi:10.1038/s41586-020-2990-5 · Cited by 68 · see citing works
Coiled coil-based therapeutics and drug delivery systems.
Utterström, J., Naeimipour, S., Selegård, R., & Aili, D. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.12.012 · Cited by 68 · cited 1× · see citing works
“Such an article would be redundant because many excellent reviews are already available (8 – 14), as are others covering newer topics such as the applications of natural and designed coiled coils in biotechnology and synthetic biology (15 – 18).”
Peptide-PAINT Super-Resolution Imaging Using Transient Coiled Coil Interactions
Eklund, A. S., Ganji, M., Gavins, G. C., et al. (2020) · Nano Letters · doi:10.1021/acs.nanolett.0c02620 · Cited by 68 · cited 1× · see citing works
“PDB, Protein Data Bank. as “ peptide-PAINT ” or “ live-PAINT ” for high-resolution light microscopy (131, 132); and targeting natural coiled coils in vitro and in cells (133 – 137).”
Reinke, A. W., Grigoryan, G., & Keating, A. E. (2010) · Biochemistry · doi:10.1021/bi902065k · Cited by 67 · see citing works
De novo design of discrete, stable 310-helix peptide assemblies
Kumar, P., Paterson, N. G., Clayden, J., & Woolfson, D. N. (2022) · Nature · doi:10.1038/s41586-022-04868-x · Cited by 67 · cited 3× · see citing works
“…polyproline-II helix followed packing with an α helix (290); three hetero-oligomeric coiled coils formed from acidic (A, red ) and basic (B, blue ) peptide chains (92, 119); an 8-helix bundle formed exclusively from 3 10 helices (52); and a single-chain 4-helix coiled coil based on apCC-Tet* (148).”
InfluentialSelf-citationStructural basis of IL-23 antagonism by an Alphabody protein scaffold
Desmet, J., Verstraete, K., Bloch, Y., Lorent, E., Wen, Y., Devreese, B. V., Vandenbroucke, K., Loverix, S., Hettmann, T., Deroo, S., et al. (2014) · Nature Communications · doi:10.1038/ncomms6237 · Cited by 66 · cited 1× · see citing works
“…coils, progress is being made here by grafting hotspot residues from natural protein – protein interactions onto nat-ural and de novo – designed coiled-coil peptides (173, 282) and by using de novo – designed, single-chain coiled coils ( “ Alpha-bodies ” ) to present binding-site libraries (283).”
Bent into shape: Folded peptides to mimic protein structure and modulate protein function
Merritt, H. I., Sawyer, N., & Arora, P. S. (2020) · Peptide Science · doi:10.1002/pep2.24145 · Cited by 65 · cited 2× · see citing works
“Of course, along with other challenges (280, 281), rigid coiled-coil scaffolds may not be optimal for binding.”
Coiled-coil assembly by peptides with non-heptad sequence motifs
Hicks, M. R., Holberton, D. V., Kowalczyk, C., & Woolfson, D. N. (1997) · Folding and Design · doi:10.1016/s1359-0278(97)00021-7 · Cited by 64 · cited 1× · see citing works
“Possibilities here include nature ’ s inclusion of nonheptad sequence repeats (55, 56) and so-called trigger sequences for folding (277 – 279).”
Self-citationSelf-sorting heterodimeric coiled coil peptides with defined and tuneable self-assembly properties
Aronsson, C., Dånmark, S., Zhou, F., Öberg, P. Å., Enander, K., Su, H., & Aili, D. (2015) · Scientific Reports · doi:10.1038/srep14063 · Cited by 63 · cited 1× · see citing works
“Applications by others of CC-Di-AB include the following: designing self-sorting heterodimers (184); developing a fl uorescence-quencher pair that reports on coiled-coil stability and orientation (185) and, similarly, coassembled fl uorescent proteins (186); constructing synthetic virus-like capsids…”
De Novo-Designed α-Helical Barrels as Receptors for Small Molecules.
Thomas, F., Dawson, W., Lang, E. J. M., Burton, A. J., Bartlett, G. J., Rhys, G. G., Mulholland, A., & Woolfson, D. (2018) · ACS Synthetic Biology · doi:10.1021/acssynbio.8b00225 · Cited by 63 · cited 1× · see citing works
“…to effect ester hydrolysis; developing receptors for reporters dyes and lipophilic biomarkers that bind within the channels with μ M af fi nities (179) and using this as the basis for a differential biosensor (180); redesigning water-soluble α HBs to produce a membrane-spanning ion channel with…”
Self-citationHagelueken, G., Clarke, B. R., Huang, H., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2935 · Cited by 62 · cited 2× · see citing works
“I would like to fi nish with an example of a coiled coil as a molecular ruler (276).”
The solution structure of a leucine-zipper motif peptide
Saudek, V., Pastore, A., Morelli, M. A. C., et al. (1991) · Protein Engineering Design and Selection · doi:10.1093/protein/4.5.519 · Cited by 62 · see citing works
Oi, C., Gidden, Z., Holyoake, L. V., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-01188-6 · Cited by 62 · cited 1× · see citing works
“PDB, Protein Data Bank. as “ peptide-PAINT ” or “ live-PAINT ” for high-resolution light microscopy (131, 132); and targeting natural coiled coils in vitro and in cells (133 – 137).”
Crystal structure of a designed, thermostable, heterotrimeric coiled coil
Nautiyal, S., & Alber, T. (1999) · Protein Science · doi:10.1110/ps.8.1.84 · Cited by 61 · cited 1× · see citing works
“Previously, with Alber, we had used the idea of electrostatic hetero-speci fi cation in computational design to make a hetero-trimer, CC-Tri-ABC (120), a structure for which was later determined by X-ray crystallography, Figure 4 (121).”
ISAMBARD: an open-source computational environment for biomolecular analysis, modelling and design
Wood, C. W., Heal, J. W., Thomson, A. R., Bartlett, G. J., Ibarra, A. Á., Brady, R. L., Sessions, R. B., & Woolfson, D. N. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx352 · Cited by 61 · cited 3× · see citing works
“Some allow coiled-coil backbones to be built quickly and accurately (28, 31), and others allow full atomistic modeling of coiled coils including side chains (29, 33, 35, 36).”
Self-citationPeptide Assembly Directed and Quantified Using Megadalton DNA Nanostructures
Jin, J., Baker, E. G., Wood, C. W., Bath, J., Woolfson, D. N., & Turberfield, A. J. (2019) · ACS Nano · doi:10.1021/acsnano.9b04251 · Cited by 60 · cited 1× · see citing works
“…transcription factors (119, 170) and cytoscaffolds (171) that assemble and function in bacterial cells; the directed assembly of large DNA origamis (172); the presentation of functioning hotspot residues from natural protein – protein interactions (173); the direction of protein – protein…”
Self-citationGeneralized Crick Equations for Modeling Noncanonical Coiled Coils
Offer, G., Hicks, M. R., & Woolfson, D. N. (2002) · Journal of Structural Biology · doi:10.1006/jsbi.2002.4448 · Cited by 59 · cited 1× · see citing works
“Some allow coiled-coil backbones to be built quickly and accurately (28, 31), and others allow full atomistic modeling of coiled coils including side chains (29, 33, 35, 36).”
Self-citationNegron, C., & Keating, A. E. (2014) · Journal of the American Chemical Society · doi:10.1021/ja507847t · Cited by 59 · cited 1× · see citing works
“…at e , similar to so-called Alacoils (151); a preference for Gln at g ; and the use of charge complementarity at b & c as a fi nal guide to helix-helix speci fi cation and orientation, and speci fi cally, using oppositely charged residues in the N-and C-terminal halves of these designs (152 – 154).”
Wang, F., Gnewou, O. M., Modlin, C., Beltrán, L. C., Xu, C., Su, Z., Juneja, P., Grigoryan, G., Egelman, E. H., & Conticello, V. P. (2021) · Nature Communications · doi:10.1038/s41467-020-20689-w · Cited by 59 · see citing works
Self-assembled protein nanocarrier for intracellular delivery of antibody
Lim, S. I., Lukianov, C. I., & Champion, J. A. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.01.007 · Cited by 57 · cited 1× · see citing works
“Finally, in an impressive series of studies, Champion et al. have shown that the original CC-Hex sequence can be complexed with IgG to promote the cellular uptake and cytosolic delivery of these antibodies (220 – 223).”
Jiang, X., Ho, D. B. T., Mahe, K., Mia, J., Sepulveda, G., Antkowiak, M., Jiang, L., Yamada, S., & Jao, L.-E. (2021) · Journal of Cell Science · doi:10.1242/jcs.258897 · Cited by 57 · see citing works
The Native GCN4 Leucine-Zipper Domain Does Not Uniquely Specify a Dimeric Oligomerization State
Oshaben, K. M., Salari, R., McCaslin, D. R., Chong, L. T., & Horne, W. S. (2012) · Biochemistry · doi:10.1021/bi301132k · Cited by 55 · cited 1× · see citing works
“This was motivated by much of the work to that point being done on the GCN4-p1 system, which increasingly revealed contexts and alternate states that thwarted systematic studies (73, 75, 113).”
Engineering protein stability with atomic precision in a monomeric miniprotein
Baker, E. G., Williams, C., Hudson, K. L., Bartlett, G. J., Heal, J. W., Goff, K. L. P., Sessions, R. B., Crump, M. P., & Woolfson, D. N. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2380 · Cited by 55 · cited 1× · see citing works
“…from ≈ 5 to 10 Å. Bottom row from left to right : a monomeric single-chain miniprotein with a polyproline-II helix followed packing with an α helix (290); three hetero-oligomeric coiled coils formed from acidic (A, red ) and basic (B, blue ) peptide chains (92, 119); an 8-helix bundle formed…”
Self-citationMolecular architecture of the autoinhibited kinesin-1 lambda particle
Weijman, J. F., Yadav, S. K. N., Surridge, K. J., Cross, J. A., Borucu, U., Mantell, J., Woolfson, D. N., Schaffitzel, C., & Dodding, M. P. (2022) · Science Advances · doi:10.1126/sciadv.abp9660 · Cited by 54 · see citing works
Self-citationHow to untwist an α-helix: structural principles of an α-helical barrel11Edited by J. Thornton
Calladine, C. R., Sharff, A., & Luisi, B. F. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.4320 · Cited by 51 · cited 1× · see citing works
“The resulting helices are no longer simple amphiphiles, they are bifaceted with the potential to form high-order structures (97, 99, 101, 102).”
Dn-symmetrical tertiary templates for the design of tubular proteins11Edited by J. Thornton
North, B., Summa, C. M., Ghirlanda, G., & DeGrado, W. F. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4900 · Cited by 51 · cited 3× · see citing works
“The idea that residues at e and g sites progressively become involved in coiled-coil interfaces with increasing oligomeric state was fi rst formalized by Wal-shaw (96, 97), though Dunker and Zaleske considered the more general problem earlier (98), as did DeGrado et al. (99) at about the same time as Walshaw.”
Carbon Nanotubes Encapsulated in Coiled‐Coil Peptide Barrels
Mann, F. A., Horlebein, J., Meyer, N. F., Meyer, D., Thomas, F., & Kruss, S. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201800993 · Cited by 51 · cited 1× · see citing works
“…direct the assembly of reversible protein condensates in living cells (213, 214); to encapsulate carbon nanotubes with these water-soluble peptides (215); to explore valency effects in natural protein – protein interactions, e.g. , galectin-glycan binding (216); to develop Spy&Go, augmenting the…”
Kumar, P., & Woolfson, D. N. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab631 · Cited by 51 · cited 1× · see citing works
“Panels B and C are adapted from Walshaw and Woolfson (2003) (96) with permission. structures parametrically and energetically (32, 37 – 39).”
Self-citationOpen‐and‐shut cases in coiled‐coil assembly: α‐sheets and α‐cylinders
Walshaw, J., & Woolfson, D. N. (2001) · Protein Science · doi:10.1110/ps.36901 · Cited by 50 · cited 2× · see citing works
“…residues at e and g sites progressively become involved in coiled-coil interfaces with increasing oligomeric state was fi rst formalized by Wal-shaw (96, 97), though Dunker and Zaleske considered the more general problem earlier (98), as did DeGrado et al. (99) at about the same time as Walshaw.”
Self-citationDe novo coiled-coil peptides as scaffolds for disrupting protein–protein interactions
Fletcher, J. M., Horner, K. A., Bartlett, G. J., Rhys, G. G., Wilson, A. J., & Woolfson, D. N. (2018) · Chemical Science · doi:10.1039/c8sc02643b · Cited by 50 · cited 2× · see citing works
“…coils, progress is being made here by grafting hotspot residues from natural protein – protein interactions onto nat-ural and de novo – designed coiled-coil peptides (173, 282) and by using de novo – designed, single-chain coiled coils ( “ Alpha-bodies ” ) to present binding-site libraries (283).”
Self-citationCoiled coils 9-to-5: rational de novo design of α-helical barrels with tunable oligomeric states
Dawson, W., Martin, F. J. O., Rhys, G. G., Shelley, K. L., Brady, R. L., & Woolfson, D. N. (2021) · Chemical Science · doi:10.1039/d1sc00460c · Cited by 50 · see citing works
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- Plaper, 2021, De novo designed parallel heterodimeric coiled-coil peptide pairs with high affinity for use in mammalian cells, FEBS Open Biol., 11, 269
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De novo protein design—From new structures to programmable functions
Kortemme, T. (2024) · Cell · doi:10.1016/j.cell.2023.12.028 · Cited by 361 · see citing works
“Generalizing this idea, a systematic exploration of alpha-helical coiled-coils led to the design of novel architectures and development of principles to exploit these architectures for diverse functions 55 .”
An atlas of protein homo-oligomerization across domains of life
Schweke, H., Pacesa, M., Levin, T., Goverde, C. A., Kumar, P., Duhoo, Y., Dornfeld, L. J., Dubreuil, B., Georgeon, S., Ovchinnikov, S., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.022 · Cited by 144 · see citing works
Self-citationBlueprinting extendable nanomaterials with standardized protein blocks
Huddy, T. F., Hsia, Y., Kibler, R. D., Xu, J., Bethel, N. P., Nagarajan, D., Redler, R. L., Leung, P. J. Y., Weidle, C., Courbet, A., et al. (2024) · Nature · doi:10.1038/s41586-024-07188-4 · Cited by 68 · see citing works
“There is a rich history of designing coiled coils using simple geometric principles; this extensibility and designability have made them widely used constituents of designed protein materials 15 .”
Coiled-coil domains are sufficient to drive liquid-liquid phase separation in protein models
Ramirez, D. A., Hough, L. E., & Shirts, M. R. (2024) · Biophysical Journal · doi:10.1016/j.bpj.2024.02.007 · Cited by 55 · see citing works
Diversity of Bioinspired Hydrogels: From Structure to Applications
Lupu, A., Grădinaru, L. M., Grădinaru, V. R., & Bercea, M. (2023) · Gels · doi:10.3390/gels9050376 · Cited by 47 · see citing works
“Many efforts have been focused on peptides folding into β-sheets (amyloid-like structures [22]) and also on the rational design of α-helical folding (proteins/peptide stabilization) [23].”
BackgroundCoCoNat: a novel method based on deep learning for coiled-coil prediction
Madeo, G., Savojardo, C., Manfredi, M., Martelli, P. L., & Casadio, R. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad495 · Cited by 38 · see citing works
“The input of this network is built based on a well-known biophysical feature: the oligomeric state of canonical CCD is largely determined by the nature of hydrophobic residues in the heptad repeat pattern, namely, residues labelled with registers a and d (see Woolfson, 2023).”
BackgroundDe novo design and structure of a peptide–centric TCR mimic binding module
Householder, K. D., Xiang, X., Jude, K. M., Deng, A., Obenaus, M., Zhao, Y., Wilson, S. C., Chen, X. T., Wang, N., & García, K. C. (2025) · Science · doi:10.1126/science.adv3813 · Cited by 43 · see citing works
“…probes or therapeutics. α -helical bundles offer several advantages over antibodies: they are compact, modular, and present amino acid side chains on a rigid platform (26), reducing the design complexity observed with flexible complementarity-determining region (CDR) loops on antibodies.”
Undheim, T. A. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1359768 · Cited by 33 · see citing works
“…achieved near-perfect protein fold predictions, it was the most important moment for AI in science so far, yet left plenty of work for structural biology (Perrakis and Sixma, 2021), including the application of coiled coils as a self-assembly building block in synthetic biology (Woolfson, 2023).”
BackgroundRationally seeded computational protein design of ɑ-helical barrels
Albanese, K. I., Petrenas, R., Pirro, F., Naudin, E. A., Borucu, U., Dawson, W., Scott, D. A., Leggett, G. J., Weiner, O. D., Oliver, T. A. A., et al. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01642-0 · Cited by 25 · see citing works
“Over the past decade, a range of oligomeric α-helical barrels have been designed based on self-assembling peptides that encode highly specific and stable coiled-coil interactions 33,34 .”
InfluentialSelf-citationMadaj, R., Martinez‐Goikoetxea, M., Kaminski, K., Ludwiczak, J., & Dunin‐Horkawicz, S. (2025) · Protein Science · doi:10.1002/pro.5244 · Cited by 23 · see citing works
“Coiled coils are protein structural motifs consisting of two or more α -helices, oriented parallel or antiparallel, that wind around a central axis to form rod-like bundles (Lupas et al., 2017; Woolfson, 2023).”
A de novo designed coiled coil-based switch regulates the microtubule motor kinesin-1
Cross, J. A., Dawson, W., Shukla, S., Weijman, J. F., Mantell, J., Dodding, M. P., & Woolfson, D. N. (2024) · Nature Chemical Biology · doi:10.1038/s41589-024-01640-2 · Cited by 19 · see citing works
Self-citationComputational Prediction of Coiled–Coil Protein Gelation Dynamics and Structure
Britton, D., Christians, L. F., Liu, C., Legocki, J., Xiao, Y., Meleties, M., Yang, L., Cammer, M., Jia, S., Zhang, Z., et al. (2023) · Biomacromolecules · doi:10.1021/acs.biomac.3c00968 · Cited by 18 · see citing works
Rational Design Principles for De Novo α-Helical Peptide Barrels with Dynamic Conductive Channels
Niitsu, A., Thomson, A. R., Scott, A. J., Sengel, J. T., Jung, J., Mahendran, K. R., Sodeoka, M., Bayley, H., Sugita, Y., Woolfson, D. N., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c13933 · Cited by 19 · see citing works
Self-citationChen, X., Cai, X., Guo, P., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202315296 · Cited by 16 · see citing works
Crystal Structure of de Novo Designed Coiled-Coil Protein Origami Triangle
Satler, T., Hadži, S., & Jerala, R. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c05531 · Cited by 16 · see citing works
Design of Functional Globular β‐Sheet Miniproteins
Pham, T. L., & Thomas, F. (2024) · ChemBioChem · doi:10.1002/cbic.202300745 · Cited by 15 · see citing works
Bielska, W., Jaszczyszyn, I., Dudzic, P., Janusz, B., Chomicz, D., Wrobel, S., Greiff, V., Feehan, R., Adolf‐Bryfogle, J., & Krawczyk, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1571371 · Cited by 16 · see citing works
The art of designed coiled-coils for the regulation of mammalian cells
Plaper, T., Rihtar, E., Ramuta, T. Ž., Forstnerič, V., Jazbec, V., Ivanovski, F., Benčina, M., & Jerala, R. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.06.001 · Cited by 14 · see citing works
Design of Coiled-Coil Protein Nanostructures for Therapeutics and Drug Delivery
Britton, D., Sun, J. W., Renfrew, P. D., & Montclare, J. K. (2024) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-100722-122348 · Cited by 17 · see citing works
Injectable Thermo-Responsive Peptide Hydrogels and Its Enzyme Triggered Dynamic Self-Assembly
Yin, B., Wang, R., Guo, Y. H., Li, L., & Hu, X. (2024) · Polymers · doi:10.3390/polym16091221 · Cited by 13 · see citing works
Strategies and Applications for Supramolecular Protein Self‐Assembly
Li, Y., Tian, R., Zou, Y., Wang, T., & Liu, J. (2024) · Chemistry - A European Journal · doi:10.1002/chem.202402624 · Cited by 13 · see citing works
Co-translational ribosome pairing enables native assembly of misfolding-prone subunits
Wruck, F., Schmitt, J. L., Till, K., Fenzl, K., Bertolini, M., Tippmann, F., Katranidis, A., Bukau, B., Krämer, G., & Tans, S. J. (2025) · Nature Communications · doi:10.1038/s41467-025-61500-y · Cited by 13 · see citing works
“Coiled-coils have a packing arrangement termed knobs-into-holes (KIH) 34 – 36 , with certain residues like Leucine, Valine, and Isoleucine packing particularly well within this arrangement considering their side chain packing geometries 37,38 .”
Proteomimetic Strategy for the Modulation of Intrinsically Disordered Protein MYC
Nguyễn, T. T., Hong, S. H., & Arora, P. S. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c18144 · Cited by 12 · see citing works
Sučec, I., Mammeri, N. E., Dregni, A. J., et al. (2023) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.3c05295 · Cited by 12 · see citing works
Kumar, P., Petrenas, R., Dawson, W. M., Schweke, H., Levy, E. D., & Woolfson, D. N. (2023) · Protein Science · doi:10.1002/pro.4789 · Cited by 11 · see citing works
“Indeed, structure, design, and engineering studies of CCs are relatively mature and have been reviewed extensively (Hartmann, 2017; Korendovych & DeGrado, 2020; Lapenta et al., 2018; Lupas et al., 2017; Lupas & Bassler, 2017; Woolfson, 2017, 2023).”
BackgroundSelf-citationHernandez, G., Martins, M. L., Fernandes, N. P., Veloso, T., Lopes, J., Gomes, T., & Cordeiro, T. N. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf502 · Cited by 12 · see citing works
“This pattern often encodes for amphipathic α -helices, which assemble into CCs to bury the hydrophobic surface formed by the residues in positions a and d [ 86 ].”
Jha, K., Jaishwal, P., Yadav, T. P., & Singh, S. P. (2024) · Biophysical Chemistry · doi:10.1016/j.bpc.2024.107375 · Cited by 10 · see citing works
Assembly of peptide nanostructures with controllable sizes
Cheng, D., Jia, F., Jiang, Y., Conticello, V. P., & Jiang, T. (2023) · Nano Research · doi:10.1007/s12274-023-5970-x · Cited by 9 · see citing works
Hierarchical Assembly of Conductive Fibers from Coiled-Coil Peptide Building Blocks
Grosvirt-Dramen, A., Urbach, Z. J., Hurst, P. J., et al. (2025) · ACS Nano · doi:10.1021/acsnano.4c17248 · Cited by 8 · see citing works
Grafted Coiled-Coil Peptides as Multivalent Scaffolds for Protein Recognition
Acevedo‐Jake, A. M., Mylemans, B., Kay, D. F., Zhang, P., Korona, B., Rhys, G. G., Leney, A. C., Huang, D. T. C., Edwards, T. A., Itzhaki, L. S., et al. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.5c00137 · Cited by 9 · see citing works
Self-citationFountain, A. J., Böhning, J., McLaughlin, S. H., Morgan, T. E., Edelstein, P. H., Troll, M. A., Lamers, M. H., Bharat, T. A. M., Luisi, B. F., & Ramakrishnan, L. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2516660122 · Cited by 7 · see citing works
Modular Tunable α‐Helical Peptide Hydrogels for Neuronal Cells
Scott, D. A., Wasmuth, A., Abelardo, E., Hudson, K. L., Thomson, A. R., Birchall, M., Mehrban, N., Henley, J. M., & Woolfson, D. N. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202410333 · Cited by 6 · see citing works
Self-citationCao, J., Yu, Y., Han, K., Wang, B., Ma, B., Zhang, L., Sun, B., Li, Y., Li, J., Ma, Y., et al. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202507700 · Cited by 7 · see citing works
A look beyond the QR code of SNARE proteins
Yadav, D., Hacisuleyman, A., Dergai, M., Khalifeh, D., Abriata, L. A., Peraro, M. D., & Fasshauer, D. (2024) · Protein Science · doi:10.1002/pro.5158 · Cited by 6 · see citing works
“…C = O groups, while the helices are held together by hydrophobic interactions in the core (Apostolovic et al., 2010; Grigoryan & Keating, 2008; Lupas & Bassler, 2017; Mason & Arndt, 2004; Schreiber & Keating, 2011; Truebestein & Leonard, 2016; Woolfson, 2005; Woolfson, 2023; Zhang et al., 2009).”
BackgroundShaping Peptide Assemblies Using Multifaceted Cyclic Tectons
Wang, C., Lu, D., Li, J., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c04788 · Cited by 5 · see citing works
Resolving the structure and assembly of the honeybee silk heterotetrameric coiled coil
Johnston, C. L., Jobichen, C., Briggs, L. J., et al. (2025) · Protein Science · doi:10.1002/pro.70230 · Cited by 5 · see citing works
“Formation of the structure is driven by a seven-residue repeat in the amino acid sequence ( abcdefg ) where the first ( a ) and fourth ( d ) residues generally are more apolar hydrophobic than the others and form the hydrophobic core of the coiled coil (Woolfson 2023).”
Chubb, J. J., Boyle, A. L., & Albanese, K. I. (2026) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2026.103224 · Cited by 5 · see citing works
Building tailor-made bioenergetic proteins and circuits from de novo redox proteins
Hardy, B. J., Bungay, E. L., Mellor, C., Curnow, P., & Anderson, J. L. R. (2024) · Current Opinion in Electrochemistry · doi:10.1016/j.coelec.2024.101541 · Cited by 5 · see citing works
De novo designed 3-helix bundle peptides and proteins with controlled topology and stability
Leng, X., Albanese, K. I., Golub, L. R., Norman, A. A., Clayden, J., & Woolfson, D. N. (2025) · Chemical Science · doi:10.1039/d5sc05576h · Cited by 6 · see citing works
Self-citationNunes, L. O. (2026) · European Biophysics Journal · doi:10.1007/s00249-025-01810-7 · Cited by 4 · see citing works
“This corresponds to approximately between 16 and 22 amino acid residues in an α-helical conformation (Woolfson 2023) or could be one peptide of the same length in an extended conformation.”
Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assemblies
Kurgan, K. W., Martin, F. J. O., Dawson, W., Brunnock, T., Orr‐Ewing, A. J., & Woolfson, D. N. (2024) · Chemical Science · doi:10.1039/d4sc06329e · Cited by 4 · see citing works
Self-citationDe Novo Design of Parallel and Antiparallel A3B3 Heterohexameric α-Helical Barrels
Chubb, J. J., Albanese, K. I., Rodger, A., & Woolfson, D. N. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00584 · Cited by 4 · see citing works
“4,8,9,11 These rules are exemplified in the next section for hexameric barrels.”
Self-citationCoupling of Spectrin Repeat Modules for the Assembly of Nanorods and Presentation of Protein Domains
Mezgec, K., Snoj, J., Ulčakar, L., Ljubetič, A., Tušek-Žnidarič, M., Škarabot, M., & Jerala, R. (2024) · ACS Nano · doi:10.1021/acsnano.4c07701 · Cited by 3 · see citing works
“47,48 Other positions of the heptad repeat ( b , c , and f ) are usually occupied by residues with high helical propensity that may form intramolecular salt bridges, contributing to thermodynamic stability.”
BackgroundMethodIn‐Depth Structural Analysis of a Stapled Pentapeptide and Its Assembly Into Straight α‐Helices
Liu, J., Sun, J., Yang, F., Tian, Z., Wan, C., Yin, F., Ye, Y., & Li, Z. (2024) · Small · doi:10.1002/smll.202406214 · Cited by 4 · see citing works
Fountain, A. J., Böhning, J., McLaughlin, S. H., Morgan, T. E., Edelstein, P. H., Troll, M. A., Lamers, M. H., Bharat, T. A. M., Luisi, B. F., & Ramakrishnan, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.24.661325 · Cited by 4 · see citing works
Rapid Assessment of Chemical Complementarity of Ligands for Protein DesignPreprint
Petrenas, R., Ożga, K., Chubb, J. J., Romanyuk, A. V., Alibhai, D., McManus, J. J., Leggett, G. J., Scrutton, N. S., Oliver, T. A. A., & Woolfson, D. N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.30.662286 · Cited by 4 · see citing works
“Coiled-coil proteins and protein-protein interfaces are ubiquitous in nature 21 , and are amongst the most successful de novo designed proteins targeted to date 22,23 .”
Self-citationNotari, E., Wood, C. W., & Michel, J. (2025) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.4c01695 · Cited by 4 · see citing works
Design principles of the common Gly-X6-Gly membrane protein building block
Golden, K., Avarvarei, C., Anderson, C. T., Holcomb, M., Tang, W., Dai, X., Zhang, M., Maillie, C. A., Sanchez, B. B., Chen, J. S., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2503134122 · Cited by 3 · see citing works
“…compatible at intervening helix - turns among designs, evaluating this 3D packing quality within its structural context may be more predictive than simplified sequence - based rules—differing from soluble and TM coiled - coils with strict, clear patterns (e.g. beta - branching) ( 38 , 57 , 58 ).”
Insights into the Structure of Intermediate Filaments
Eibauer, M., & Medalia, O. (2026) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-032-05273-5_6 · Cited by 3 · see citing works
Chen, X., Cai, X., Guo, P., et al. (2023) · Angewandte Chemie · doi:10.1002/ange.202315296 · Cited by 3 · see citing works
Price, J. L. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c06974 · Cited by 3 · see citing works
Guo, P., Zhang, X., Chen, J., et al. (2024) · Nano Letters · doi:10.1021/acs.nanolett.4c02370 · Cited by 3 · see citing works
Si, W., Chen, H., & Wu, G. (2025) · Physical Chemistry Chemical Physics · doi:10.1039/d5cp01017a · Cited by 2 · see citing works
Hadley, K., Ricci, M., Hanževački, M., Bernstein, H., Jayasekera, H. S., Leney, A. C., Mulholland, A. J., Carniato, F., Botta, M., Britton, M. M., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c13620 · Cited by 6 · see citing works
Nonspecific interactions can lead to liquid-liquid phase separation in coiled-coil protein models
Ramirez, D. A., Shrimpton, A., Shirts, M. R., et al. (2025) · Biophysical Journal · doi:10.1016/j.bpj.2025.11.027 · Cited by 2 · see citing works
Peng, R., Santos, H. J., & Nozaki, T. (2026) · Nature Communications · doi:10.1038/s41467-026-70847-9 · Cited by 2 · see citing works
“One possible explanation for the selective secretion or surface access of KERP2 is its preferential association with anionic membrane interfaces, potentially driven by its strongly positively charged surface 34,35 .”
Five questions on the cell-to-cell movement of Orthotospoviruses
Singh, P., Raj, R., & Savithri, H. S. (2024) · BBA Advances · doi:10.1016/j.bbadva.2024.100124 · Cited by 2 · see citing works
“Coiled-coil domains harbour amphipathic α -helices with heptad repeats [34].”
BackgroundWatanabe, Y., Okafuji, I., Tamai, S., Hosokawa, N., Ohbayashi, T., Kato, S., Ito, K., Kawano, M., & Ohshima, Y. (2024) · Journal of Immunological Methods · doi:10.1016/j.jim.2024.113773 · Cited by 2 · see citing works
De novo design of α-helical peptide channels with designer stoichiometryPreprint
Niitsu, A., Thomson, A. R., Scott, A. J., Sengel, J. T., Jung, J., Mahendran, K. R., Sodeoka, M., Bayley, H., Sugita, Y., Woolfson, D. N., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.05.616771 · Cited by 2 · see citing works
Self-citationMaking Sense of Helices: Right and Wrong Models in Science and Art
Egli, M., & Zhang, S. (2023) · Molecular Frontiers Journal · doi:10.1142/s2529732523500086 · Cited by 1 · see citing works
Cavini, Í. A., Winter, A. J., Pereira, H. D., Woolfson, D. N., Crump, M. P., & Garratt, R. C. (2023) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798323006514 · Cited by 1 · see citing works
Self-citationDalley, N. A., Stern, K. L., Kitchen, R. R., Lloyd, K. B., & Price, J. L. (2023) · Peptide Science · doi:10.1002/pep2.24336 · Cited by 1 · see citing works
Szefczyk, M., Szulc, N., Bystranowska, D., Szczepańska, A., Pérez, J. L., Dudek, A., Pawlak, A., Ożyhar, A., & Berlicki, Ł. (2025) · Journal of Materials Chemistry B · doi:10.1039/d5tb00752f · Cited by 1 · see citing works
Kurokawa, M., Nakagawa, S., & Tamura, A. (2025) · Biophysical Chemistry · doi:10.1016/j.bpc.2025.107456 · Cited by 1 · see citing works
Oylumluoğlu, G. (2025) · Biosystems · doi:10.1016/j.biosystems.2025.105492 · Cited by 1 · see citing works
Domain acquisition enabled functional expansion of the TFIIS transcription factor family
Matveyeva, K., de Diego, A. S., García-López, M. Á., Gutiérrez, J., Fischer, T., & van Wely, K. H. M. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01423-9 · Cited by 1 · see citing works
Anfu, P. K., Madjitey, G., Afreh, J., Abakah, A., Dunyo, P., Manu, P., Gyasi, K. F., Osei‐Poku, P., & Kwarteng, A. (2025) · Medicine Advances · doi:10.1002/med4.70027 · Cited by 1 · see citing works
“Figure 3 shows alpha helices outnumbering beta strands, contributing to molecular rigidity and stability through hydrogen bonding and dipole moment neutralization [32].”
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Assembly of a protein-mimetic helical metal–organic framework for enantioseparation
Tu, S., Qi, J., Li, W., Chen, W., Ma, X., Wang, K., Wang, Z.-Y., Li, M., Wu, X., & Zhu, C. (2026) · Inorganic Chemistry Frontiers · doi:10.1039/d6qi00435k · Cited by 1 · see citing works
Enzyme-Free Phosphorylation with Kinetic Gating in a De Novo Coiled-Coil System
Poprawa, S., Hoja, N., Hipp, C., King, R. O., Soria‐Carrera, H., Woolfson, D. N., Sattler, M., Kaila, V. R. I., & Boekhoven, J. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c02162 · Cited by 1 · see citing works
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De novo grafted coiled-coil peptides as p53/ h DM2 inhibitors
Spain, F., Giménez, D., Acevedo‐Jake, A. M., Mylemans, B., Brooks, N. J., Korona, B., Huang, D. T. C., Edwards, T. A., Leney, A. C., Itzhaki, L. S., et al. (2026) · RSC Chemical Biology · doi:10.1039/d6cb00063k · Cited by 1 · see citing works
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“This distribution is crucial for a protein’s function, hence for the function of our designed vaccine [89].”
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“The glutamic acid residue is not typical for position a of a coiled-coil-forming heptad sequence, because residues at position a normally contribute to forming a hydrophobic core (Woolfson, 2023).”
BackgroundReynolds, M. F. (2024) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2024.112642 · Cited by 1 · see citing works
High‐Throughput Evaluation of Natural Diversity of F‐Type ATP Synthase Rotor Ring Stoichiometries
Osipov, S. D., Zinovev, E. V., Anuchina, A. A., Kuzmin, A., Minaeva, A. V., Ryzhykau, Y. L., Vlasov, A. V., & Gushchin, I. (2025) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26790 · Cited by 2 · see citing works
Rationally seeded computational protein designPreprint
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Self-citationCOCONUT: An analysis of coiled-coil regions in proteinsPreprint
Soni, N., & Madhusudhan, M. S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.25.586698 · Cited by 2 · see citing works
“The characteristic heptad sequence repeat pattern (a-b-c-d-e-f-g) shapes their overall structure, with the residues at heptad positions 'a' and 'd' forming a buried interface, while residues at other positions are exposed to the solvent (15, 16).”
BackgroundBiomolecular condensation using de novo designed globular proteinsPreprint
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Self-citationCoiled-coil scaffolds for Targeted Protein DegradationPreprint
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“1a ), and we demonstrate how target-binding and degradation ligands can be integrated within single polypeptide chains using bifunctional de novo coiled-coil modules 26 .”
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“More details can be found in reviews 10,68,69 and successful design examples 70–73 .”
Self-citationProteomics and the techniques applicable
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Exchange, promiscuity, and orthogonality in de novo designed coiled-coil peptide assembliesPreprint
Kurgan, K. W., Martin, F. J. O., Dawson, W., Brunnock, T., Orr‐Ewing, A. J., & Woolfson, D. N. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.01.610678
“16,30,32,33,57 Moreover, the g à f heptad repeats are similar, i.e. g LKEIAX with g = Thr for CC-Pent2, Ser for CC-Hex2, and Ala for CC-Hept.”
BackgroundSelf-citationDe novo design of parallel and antiparallel A 3 B 3 heterohexameric α-helical barrelsPreprint
Chubb, J. J., Albanese, K. I., Rodger, A., & Woolfson, D. N. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.25.614870
Self-citationShao, S., Wu, Y., Zhang, L., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062616
“The protein sequences for each gene were submitted to the website (http://www.csbio.sjtu.edu.cn/bioinf/plant-multi (accessed on 10 November 2024)) for predicting subcellular locations, following a previous study [64].”
Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switchPreprint
Shukla, S., Cross, J. A., Kish, M., Yadav, S. K. N., Weijman, J. F., O’Regan, L., Mantell, J., Borucu, U., Leng, X., Schaffitzel, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.08.647705
“This is consistent with hydrogen-bonded α-helical structure and the known stabilities of coiled-coil assemblies in general that is protective against hydrogen-exchange and may partially mask changes in solvent accessibility ( 59 ).”
Self-citationA yeast model reveals the SMAD3 nuclear import mechanismPreprint
González, D. P., Emokpae, M. C., Lusk, C. P., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.09.663975
“We believe the cell-periphery localization may be due to the 2 ⍺ -helices that resemble amphipathic helices, which are known to interact with lipid bilayers [38] .”
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Sudden Death-Associated KCNH2 Variants Have Opposing Effects on hERG1 NP FunctionPreprint
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Heptad insertion extends the E. coli ROP protein by 50 %
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Solvent-Encoded Intrinsic Emission and Self-Assembly of Coiled-Coil-Based Foldamers
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Structure and signaling mechanism of Helicobacter pylori transducer-like protein DPreprint
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Coiled-Coil Domain Kinking Controls Laminin-332 Cleavage by Elastase
Akter, L., Amyot, R., Großmann, R., Beta, C., Flechsig, H., & Franz, C. M. (2026) · Journal of Molecular Biology · doi:10.1016/j.jmb.2026.169991
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Coiled-coil homo-oligomerization and disaggregase Hsp104 act in parallel to stabilize orphan septinsPreprint
Cavini, Í. A., Yeager, R., Velasquez, A., Pinto, A. P. A., Araujo, A. P. U., Garratt, R. C., & McMurray, M. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.09.710472
Kinesin-1 conformational dynamics are controlled by a cargo-sensitive TPR switchPreprint
Shukla, S., Cross, J. A., Kish, M., Yadav, S. K. N., Weijman, J. F., O’Regan, L., Mantell, J., Borucu, U., Leng, X., Schaffitzel, C., et al. (2026) · eLife · doi:10.7554/elife.109462.2
Self-citationChirality Effect on Physical and Biological Properties of Peptide-Based Hydrogels
Rosa, L. D., D’Andrea, L. D., & Romanelli, A. (2026) · Gels · doi:10.3390/gels12050399
“In canonical coiled coils composed of L-amino acids, right-handed α -helices wrap around each other to form a left-handed supercoil [14].”
- Authors
- Woolfson, D. N.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Woolfson, Derek N.
- ORCID
- Woolfson, Derek N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2023-04
- Volume
- 299
- Issue
- 4
- Pages
- 104579
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC10124910
- OpenAlex
- W4323276421
- Semantic Scholar
- e4a88b334ce7fa373dec876f2a178f521ccd9503
- Cited by
- 106
- References
- 292
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 29 · 2023: 14
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (submittedVersion, cc-by-nc-nd)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/S002820/1, BB/V004220/1, BB/V006231/1)
- Royal Society (WM140008)
- University of Bristol
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- alpha-helical coiled coil, coiled-coil stability, synthetic biology, protein design, protein folding
- MeSH terms
- Protein Domains, Protein Conformation, alpha-Helical, Biology, Physics, Proteins, Protein Folding
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