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Understanding a protein fold: The physics, chemistry, and biology of α-helical coiled coils
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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.32,33”
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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“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]
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“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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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · cited 2×
“Moreover, I am sure that this will grow with the application of AlphaFold2 to entire proteomes and the development of AlphaFold2 Multimer (3, 4, 242).”
Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
WATSON, J. D., & CRICK, F. H. C. (1953) · Nature · doi:10.1038/171737a0 · Cited by 13,584 · cited 4×
“A particularly interesting example is the H protein from bacteriophage Φ X174, which forms a tube that is essential for the virus to infect E. coli and is believed to transfer the viral ssDNA across the host periplasm.”
InfluentialVaradi, M., Anyango, S., Deshpande, M., Nair, S., Natassia, C., Yordanova, G., Yuan, D., Stroe, O., Wood, G., Laydon, A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1061 · Cited by 7,850 · cited 2×
“Moreover, I am sure that this will grow with the application of AlphaFold2 to entire proteomes and the development of AlphaFold2 Multimer (3, 4, 242).”
Accurate prediction of protein structures and interactions using a 3-track network
Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,549
Predicting coiled coils from protein sequences.
Lupas, A., Van Dyke, M., & Stock, J. (1991) · Science · doi:10.1126/science.252.5009.1162 · Cited by 3,953
Stereochemistry of polypeptide chain configurations
Ramachandran, G. N., Ramakrishnan, C., & Sasisekharan, V. (1963) · Journal of Molecular Biology · doi:10.1016/s0022-2836(63)80023-6 · Cited by 3,651 · cited 1×
“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.”
InfluentialThe Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins
Landschulz, W. H., Johnson, P. F., & McKnight, S. L. (1988) · Science · doi:10.1126/science.3289117 · Cited by 3,443 · cited 1×
“…long fi brous coiled coils in motor proteins and intermediate fi laments (IFs), which were among the fi rst targets in structural molecular biology (21, 224); and short oligomerization domains like the leucine zippers (5), which became a model for protein folding, structure, and design (6, 7, 73).”
Highly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · cited 1×
“Moreover, I am sure that this will grow with the application of AlphaFold2 to entire proteomes and the development of AlphaFold2 Multimer (3, 4, 242).”
The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain
Pauling, L. C., Corey, R. B., & Branson, H. R. (1951) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.37.4.205 · Cited by 3,007
Receptor Binding and Membrane Fusion in Virus Entry: The Influenza Hemagglutinin
Skehel, J. J., & Wiley, D. C. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.531 · Cited by 2,706 · cited 1×
“The hemagglutinin story became more interesting as it unraveled; for example, revealing a spring-loaded switch to a longer trimeric CC leading to virus-host membrane fusion, Figure 1 D (46, 47), and targets for drug design (48, 49).”
Research works printed but not linked: 1
- 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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“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
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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 69
“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 53
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
“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
“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).”
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“…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 34
“…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).”
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“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 .”
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“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
“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 12
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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
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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
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Chen, X., Cai, X., Guo, P., et al. (2023) · Angewandte Chemie · doi:10.1002/ange.202315296 · Cited by 3
Price, J. L. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c06974 · Cited by 3
Guo, P., Zhang, X., Chen, J., et al. (2024) · Nano Letters · doi:10.1021/acs.nanolett.4c02370 · Cited by 3
Si, W., Chen, H., & Wu, G. (2025) · Physical Chemistry Chemical Physics · doi:10.1039/d5cp01017a · Cited by 2
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
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Peng, R., Santos, H. J., & Nozaki, T. (2026) · Nature Communications · doi:10.1038/s41467-026-70847-9 · Cited by 2
“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 .”
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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
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Egli, M., & Zhang, S. (2023) · Molecular Frontiers Journal · doi:10.1142/s2529732523500086 · Cited by 1
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
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
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
Kurokawa, M., Nakagawa, S., & Tamura, A. (2025) · Biophysical Chemistry · doi:10.1016/j.bpc.2025.107456 · Cited by 1
Oylumluoğlu, G. (2025) · Biosystems · doi:10.1016/j.biosystems.2025.105492 · Cited by 1
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
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
“Figure 3 shows alpha helices outnumbering beta strands, contributing to molecular rigidity and stability through hydrogen bonding and dipole moment neutralization [32].”
Imamura, I., Kawaguchi, S., Suzuki, S., Kamiya, Y., Ohnishi, Y., Ueda, J., Nashiki, K., Takegawa, K., Tabuchi, M., & Tanaka, N. (2025) · Molecular Microbiology · doi:10.1111/mmi.70033 · Cited by 1
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
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
Self-citationLiang, X.-L., Yan, J., Chen, Q.-Q., et al. (2026) · Journal of Coordination Chemistry · doi:10.1080/00958972.2026.2675380 · Cited by 1
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
Self-citationFerdousy, T. J., Miraz, M. M. H., Arian, T. A., Ullah, M. A., Risat, M. T. H., Akter, M. A., Kundu, S., Sarkar, B. K., Sarkar, A. P., Khalipha, A. B. R., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0354891 · Cited by 1
“This distribution is crucial for a protein’s function, hence for the function of our designed vaccine [89].”
Ono, S., Watabe, E., Morisaki, K., et al. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1208913 · Cited by 1
“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
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 3
Rationally seeded computational protein designPreprint
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. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.25.554789 · Cited by 1
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
“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
Romanyuk, A. V., Kumar, R. T. P., Cross, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.695468 · Cited by 1
Self-citationCoiled-coil scaffolds for Targeted Protein DegradationPreprint
Korona, B., Mylemans, B., Acevedo‐Jake, A. M., Huang, D. T., Edwards, T. A., Wilson, A. J., Woolfson, D. N., & Itzhaki, L. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.22.695764 · Cited by 1
“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 .”
Self-citationAlbanese, K. I., Barbe, S., Tagami, S., Woolfson, D. N., & Schiex, T. (2025) · Nature Reviews Methods Primers · doi:10.1038/s43586-025-00383-1 · Cited by 104
“More details can be found in reviews 10,68,69 and successful design examples 70–73 .”
Self-citationProteomics and the techniques applicable
Zargar, S. M., Farooq, A., Sofi, P. A., Sudan, J., Urwat, U., & Hussain, K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21923-8.00002-9
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., & Khokha, M. K. (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] .”
Cao, J., Yu, Y., Han, K., Wang, B., Ma, B., Zhang, L., Sun, B., Li, Y., Li, J., Ma, Y., et al. (2025) · Angewandte Chemie · doi:10.1002/ange.202507700
Sudden Death-Associated KCNH2 Variants Have Opposing Effects on hERG1 NP FunctionPreprint
Sanchez-Conde, F. G., Goodrich, M., Stack, O., Goldberg, L., Ruzycki, P., Jain, A., Jimenez-Vazquez, E. N., & Jones, D. K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.23.684168
Heptad insertion extends the E. coli ROP protein by 50 %
Karageorgos, I. L., & Gallagher, D. T. (2025) · BioDesign Research · doi:10.1016/j.bidere.2025.100061
Vidal, J., Fournet, C., Blot, M., Peris-Moreno, D., Reboud‐Ravaux, M., Taillandier, D., & Polge, C. (2025) · Results in Chemistry · doi:10.1016/j.rechem.2025.102974
Solvent-Encoded Intrinsic Emission and Self-Assembly of Coiled-Coil-Based Foldamers
Szulc, N., Wojtas, M., Kral, T. E., Pokorná, Š., Hof, M., & Szefczyk, M. (2026) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5c08320
Structure and signaling mechanism of Helicobacter pylori transducer-like protein DPreprint
Franco, K., DiIorio, M. C., Simpkin, A. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.16.699579
Nifosı̀, R., & Bellucci, L. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c02565
Liang, X.-L., Yan, J., Chen, Q.-Q., et al. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6194299
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
Sanchez-Conde, F. G., Goodrich, M. R., Stack, O., Goldberg, L., Ruzycki, P., Jain, A., Jimenez-Vazquez, E. N., & Jones, D. A. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.111296
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].”
Metadata
- 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
- Physical Sciences › Chemistry › Organic Chemistry › 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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