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Architectonic principles of polyproline II helix bundle protein domains

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Rodríguez, Cristian Segura, Laurents, Douglas V.·2024·Archives of Biochemistry and Biophysics
DOI 10.1016/j.abb.2024.109981

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Abstract

Glycine rich polyproline II helix assemblies are an emerging class of natural domains found in several proteins with different functions and diverse origins. The distinct properties of these domains relative to those composed of α-helices and β-sheets could make glycine-rich polyproline II helix assemblies a useful building block for protein design. Whereas the high population of polyproline II conformers in disordered state ensembles could facilitate glycine-rich polyproline II helix folding, the architectonic bases of these structures are not well known. Here, we compare and analyze their structures to uncover common features. These protein domains are found to be highly tolerant of distinct flanking sequences. This speaks to the robustness of this fold and strongly suggests that glycine rich polyproline II assemblies could be grafted with other protein domains to engineer new structures and functions. These domains are also well packed with few or no cavities. Moreover, a significant trend towards antiparallel helix configuration is observed in all these domains and could provide stabilizing interactions among macrodipoles. Finally, extensive networks of Cα-H···OC hydrogen bonds are detected in these domains. Despite their diverse evolutionary origins and activities, glycine-rich polyproline II helix assemblies share architectonic features which could help design novel proteins.

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Research works printed but not linked: 83

  1. Levitt, 1976, Structural patterns in globular proteins, Nature, 261, 552, 10.1038/261552a0 · DOI
  2. Baker, 2019, What has de novo protein design taught us about protein folding and biophysics?, Protein Sci., 28, 678, 10.1002/pro.3588 · DOI · Paper page
  3. Richardson, 1981, The anatomy and taxonomy of protein structure, Adv. Protein Chem., 34, 167, 10.1016/S0065-3233(08)60520-3 · DOI
  4. Laurents, 2022, AlphaFold 2 and NMR spectroscopy: partners to understand protein structure, dynamics and function, Front. Mol. Biosci., 9, 10.3389/fmolb.2022.906437 · DOI · Paper page
  5. Fraser, 1979, Chain conformation in the collagen molecule, J. Mol. Biol., 129, 463, 10.1016/0022-2836(79)90507-2 · DOI
  6. Adzhubei, 2013, Polyproline-II helix in proteins: structure and function, J. Mol. Biol., 425, 2100, 10.1016/j.jmb.2013.03.018 · DOI
  7. Cowan, 1955, The polypeptide chain configuration of collagen, Nature, 176, 1062, 10.1038/1761062a0 · DOI
  8. Tiffany, 1968, Circular dichroism of poly-L-proline in an unordered conformation, Biopolymers, 6, 1767, 10.1002/bip.1968.360061212 · DOI
  9. Tiffany, 1968, New chain conformations of poly(glutamic acid) and polylysine, Biopolymers, 6, 1379, 10.1002/bip.1968.360060911 · DOI
  10. Tiffany, 1969, Circular dichroism of a random polypeptide chain, Biopolymers, 4, 347, 10.1002/bip.1969.360080306 · DOI
  11. Tiffany, 1972, Effect of temperature on the circular dichroism spectra of polypeptides in the extended state, Biopolymers, 11, 2309, 10.1002/bip.1972.360111109 · DOI
  12. Tiffany, 1973, Extended conformations of polypeptides and proteins in urea and guanidine hydrochloride, Biopolymers, 12, 575, 10.1002/bip.1973.360120310 · DOI
  13. Shi, 2002, Polyproline II structure in a sequence of seven alanine residues, Proc. Natl. Acad. Sci. U. S. A., 99, 9190, 10.1073/pnas.112193999 · DOI
  14. Woutersen, 2000, Structure determination of trialanine in water using polarization sensitive two-dimensional vibrational spectroscopy, J. Phys. Chem. B, 104, 11316, 10.1021/jp001546a · DOI
  15. Graf, 2007, Structure and dynamics of the homologous series of alanine peptides: a joint molecular dynamics/NMR study, J. Am. Chem. Soc., 129, 1179, 10.1021/ja0660406 · DOI
  16. Pappu, 2000, The Flory isolated-pair hypothesis is not valid for polypeptide chains: implications for protein folding, Proc. Natl. Acad. Sci. U. S. A., 97, 12565, 10.1073/pnas.97.23.12565 · DOI
  17. Newberry, 2013, n→π* interactions of amides and thioamides: implications for protein stability, J. Am. Chem. Soc., 135, 7843, 10.1021/ja4033583 · DOI
  18. Mezei, 2004, Polyproline II helix is the preferred conformation for unfolded polyalanine in water, Proteins, 55, 502, 10.1002/prot.20050 · DOI
  19. Lanza, 2015, Interfacial water at the trialanine hydrophilic surface: a DFT electronic structure and bottom-up investigation, Phys. Chem. Chem. Phys., 17, 17101, 10.1039/C5CP00270B · DOI
  20. Avbelj, 2003, Role of backbone solvation and electrostatics in generating preferred peptide backbone conformations: distributions of phi, Proc. Natl. Acad. Sci. U. S. A., 100, 5742, 10.1073/pnas.1031522100 · DOI
  21. Eker, 2004, Preferred peptide backbone conformations in the unfolded state revealed by the structure analysis of alanine-based (AXA) tripeptides in aqueous solution, Proc. Natl. Acad. Sci. U. S. A., 101, 10054, 10.1073/pnas.0402623101 · DOI
  22. Andrews, 2020, Glycine in water favors the polyproline II state, Biomolecules, 10, 1121, 10.3390/biom10081121 · DOI
  23. Schweitzer-Stenner, 2023, The relevance of short peptides for an understanding of unfolded and intrinsically disordered proteins, Phys. Chem. Chem. Phys., 25, 11908, 10.1039/D3CP00483J · DOI
  24. Ma, 2001, Polyproline II helix is a key structural motif of the elastic PEVK segment of titin, Biochemistry, 40, 3427, 10.1021/bi0022792 · DOI
  25. Li, 2002, Reverse engineering of the giant muscle protein titin, Nature, 418, 998, 10.1038/nature00938 · DOI
  26. Kjaergaard, 2010, Temperature-dependent structural changes in intrinsically disordered proteins: formation of alpha-helices or loss of polyproline II?, Protein Sci., 19, 1555, 10.1002/pro.435 · DOI
  27. Si, 2016, The role of functional prion-like proteins in the persistence of memory, Cold Spring Harbor Perspect. Biol., 8, 10.1101/cshperspect.a021774 · DOI
  28. Ramírez de Mingo, 2022, Conformational dynamics in the disordered region of human CPEB3 linked to memory consolidation, BMC Biol., 20, 129, 10.1186/s12915-022-01310-6 · DOI
  29. Zhang, 2022, Possible co-evolution of polyglutamine and polyproline in huntingtin protein: proline-rich domain as transient folding chaperone, J. Phys. Chem. Lett., 13, 6331, 10.1021/acs.jpclett.2c01184 · DOI
  30. Li, 2012, Phase transitions in the assembly of multivalent signalling proteins, Nature, 483, 336, 10.1038/nature10879 · DOI
  31. Treviño, 2018, The singular NMR fingerprint of a polyproline II helical bundle, J. Am. Chem. Soc., 140, 16988, 10.1021/jacs.8b05261 · DOI
  32. Mompeán, 2021, Do polyproline II helix associations modulate biomolecular condensates?, FEBS Open Bio, 11, 2390, 10.1002/2211-5463.13163 · DOI
  33. Kar, 2021, Glycine-rich peptides from Fus have an intrinsic ability to self-assemble into fibers and networked fibrils, Biochemistry, 60, 3213, 10.1021/acs.biochem.1c00501 · DOI
  34. Russ, 2000, The GxxxG motif: a framework for transmembrane helix-helix association, J. Mol. Biol., 296, 911, 10.1006/jmbi.1999.3489 · DOI
  35. Munter, 2007, GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42, EMBO J., 26, 1702, 10.1038/sj.emboj.7601616 · DOI
  36. Rando, 2023, GxxxG motif stabilize ion-channel like pores through C(α)-H···O interaction in Aβ (1-40), Int. J. Mol. Sci., 24, 10.3390/ijms24032192 · DOI
  37. Itagaki, 2019, Sterical recognition at helix-helix interface of Leu-Aib-based polypeptides with and without a GxxxG-motif, Langmuir, 35, 7249, 10.1021/acs.langmuir.9b00620 · DOI
  38. Adzhubei, 1993, Left-handed polyproline II helices commonly occur in globular proteins, J. Mol. Biol., 229, 472, 10.1006/jmbi.1993.1047 · DOI
  39. Sreerama, 1994, Poly(pro)II helices in globular proteins: identification and circular dichroic analysis, Biochemistry, 33, 10022, 10.1021/bi00199a028 · DOI
  40. Law, 2010, The relationship between water bridges and the polyproline II conformation: a large-scale analysis of molecular dynamics simulations and crystal structures, Protein Eng. Des. Sel., 23, 27, 10.1093/protein/gzp069 · DOI
  41. Kumar, 2016, Structural and functional analyses of polyproline-II helices in globular proteins, J. Struct. Biol., 196, 414, 10.1016/j.jsb.2016.09.006 · DOI
  42. Meirson, 2021, Structural basis of SARS-CoV-2 spike protein induced by ACE2, Bioinformatics, 37, 929, 10.1093/bioinformatics/btaa744 · DOI
  43. Reid, 1976, Subunit composition and structure of subcomponent C1q of the first component of human complement, Biochem. J., 155, 19, 10.1042/bj1550019 · DOI
  44. Zairi, 2014, The collagen-like protein gp12 is a temperature-dependent reversible binder of SPP1 viral capsids, J. Biol. Chem., 289, 27169, 10.1074/jbc.M114.590877 · DOI
  45. Dvir, 2004, The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix, EMBO J., 23, 4394, 10.1038/sj.emboj.7600425 · DOI
  46. Yu, 2023, Hollow octadecameric self-assembly of collagen-like peptides, J. Am. Chem. Soc., 145, 5285, 10.1021/jacs.2c12931 · DOI
  47. Traub, 1969, Polymers of tripeptides as collagen models. V. An X-ray study of poly(L-prolyl-glycyl-glycine), J. Mol. Biol., 43, 479, 10.1016/0022-2836(69)90353-2 · DOI
  48. Lotz, 1971, The crystal structures of poly(LAla-Gly-Gly-Gly)II and Poly(LAla-Gly-Gly)II, J. Mol. Biol., 61, 195, 10.1016/0022-2836(71)90216-6 · DOI
  49. Crick, 1955, Structure of polyglycine II, Nature, 176, 780, 10.1038/176780a0 · DOI
  50. Ramachandran, 1966, Molecular structure of polyglycine II, Biochim. Biophys. Acta, 112, 168, 10.1016/S0926-6585(96)90019-9 · DOI
  51. Krimm, 1986, Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins, Adv. Protein Chem., 38, 181, 10.1016/S0065-3233(08)60528-8 · DOI
  52. Pentelute, 2008, X-ray structure of snow flea antifreeze protein determined by racemic crystallization of synthetic protein enantiomers, J. Am. Chem. Soc., 130, 9695, 10.1021/ja8013538 · DOI
  53. Scholl, 2021, Crystal waters on the nine polyproline type II helical bundle springtail antifreeze protein from Granisotoma rainieri match the ice lattice, FEBS J., 288, 4332, 10.1111/febs.15717 · DOI
  54. Buglino, 2002, Structural and biochemical analysis of the Obg GTP binding protein, Structure, 10, 1581, 10.1016/S0969-2126(02)00882-1 · DOI
  55. Kukimoto-Niino, 2004, Crystal structure of the GTP-binding protein Obg from Thermus thermophilus HB8, J. Mol. Biol., 337, 761, 10.1016/j.jmb.2004.01.047 · DOI
  56. Gkekas, 2017, Structural and biochemical analysis of Escherichia coli ObgE, a central regulator of bacterial persistence, J. Biol. Chem., 292, 5871, 10.1074/jbc.M116.761809 · DOI
  57. Mus, 2017, Structural basis for the mechanism of ATP-dependent acetone carboxylation, Sci. Rep., 7, 7234, 10.1038/s41598-017-06973-8 · DOI
  58. Warkentin, 2017, A rare polyglycine type II-like helix motif in naturally occurring proteins, Proteins, 85, 2017, 10.1002/prot.25355 · DOI
  59. Dunne, 2018, Salmonella phage S16 tail fiber adhesin features a rare polyglycine rich domain for host recognition, Structure, 26, 1573, 10.1016/j.str.2018.07.017 · DOI
  60. Reshetnyak, 2021, Mechanism for the activation of the anaplastic lymphoma kinase receptor, Nature, 600, 153, 10.1038/s41586-021-04140-8 · DOI
  61. De Munck, 2021, Structural basis of cytokine-mediated activiation of ALK family receptors, Nature, 600, 143, 10.1038/s41586-021-03959-5 · DOI
  62. Gates, 2017, Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core, Proc. Natl. Acad. Sci. U. S. A., 114, 2241, 10.1073/pnas.1609579114 · DOI
  63. Treviño, 2022, Insight into polyproline II helical bundle stability in an antifreeze protein denatured state, Biophys. J., 121, 4560, 10.1016/j.bpj.2022.10.034 · DOI
  64. Ulamec, 2020, Looking beyond the core: the role of flanking regions in the aggregation of amyloidogenic peptides and proteins, Front. Neurosci., 14, 10.3389/fnins.2020.611285 · DOI
  65. Rother, 2009, Voronoia: analyzing packing in protein structures, Nucleic Acids Res., 37, D393, 10.1093/nar/gkn769 · DOI
  66. Liang, 2001, Are proteins well-packed?, Biophys. J., 81, 751, 10.1016/S0006-3495(01)75739-6 · DOI
  67. Alexandrescu, 2001, NMR of hydrogen bonding in cold-shock protein A and an analysis of the influence of crystallographic resolution on comparisons of hydrogen bond lengths, Protein Sci., 10, 1856, 10.1110/ps.14301 · DOI
  68. Weiss, 2012, Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and genetic interactions in learning, memory and adult neurogenesis, Pharmacol. Biochem. Behav., 100, 566, 10.1016/j.pbb.2011.10.024 · DOI
  69. Hallberg, 2016, The role of the ALK receptor in cancer biology, Ann. Oncol., 27, iii4, 10.1093/annonc/mdw301 · DOI
  70. Reshetnyak, 2015, Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: hierarchy and specificity of ligand-receptor interactions, Proc. Natl. Acad. Sci. U. S. A., 112, 15862, 10.1073/pnas.1520099112 · DOI
  71. Li, 2021, Structural basis for ligand reception by anaplastic lymphoma kinase, Nature, 600, 148, 10.1038/s41586-021-04141-7 · DOI
  72. Lu, 2013, Molecular structure of β-amyloid fibrils in Alzheimer's disease brain tissue, Cell, 154, 1257, 10.1016/j.cell.2013.08.035 · DOI
  73. Di, 2009, A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis, Science, 323, 1473, 10.1126/science.1168979 · DOI
  74. Jonsson, 2012, A mutation in APP protects against Alzheimer's disease and age-related cognitive decline, Nature, 488, 96, 10.1038/nature11283 · DOI · Paper page
  75. Benilova, 2014, The Alzheimer disease protective mutation A2T modulates kinetic and thermodynamic properties of amyloid-β (Aβ) aggregation, J. Biol. Chem., 289, 30977, 10.1074/jbc.M114.599027 · DOI
  76. Graham, 2020, Antifreeze protein complements cryoprotective dehydration in the freeze-avoiding springtail Megaphorura arctica, Sci. Rep., 10, 3047, 10.1038/s41598-020-60060-z · DOI
  77. Pakula, 1990, Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface, Nature, 344, 363, 10.1038/344363a0 · DOI
  78. Huang, 2019, Impacts of the terminal charged residues on polyproline conformation, J. Phys. Chem. B, 123, 138, 10.1021/acs.jpcb.8b10864 · DOI
  79. Schell, 2006, Hydrogen bonding increases packing density in the protein interior, Proteins, 63, 278, 10.1002/prot.20826 · DOI
  80. Kuemin, 2009, Effects of terminal functional groups on the stability of the polyproline II structure: a combined experimental and theoretical study, J. Am. Chem. Soc., 131, 15474, 10.1021/ja906466q · DOI
  81. Sheridan, 1982, alpha-Helix dipole model and electrostatic stabilization of 4-alpha-helical proteins, Proc. Natl. Acad. Sci. U. S. A., 79, 4545, 10.1073/pnas.79.15.4545 · DOI
  82. Baker, 2017, Engineering protein stability with atomic precision in a monomeric miniprotein, Nat. Chem. Biol., 13, 764, 10.1038/nchembio.2380 · DOI
  83. Wu, 2023, De novo design of modular peptide-binding proteins by superhelical matching, Nature, 616, 581, 10.1038/s41586-023-05909-9 · DOI

Metadata

Authors
Rodríguez, C. S., & Laurents, D. V.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
Corresponding author
Laurents, Douglas V.
ORCID
Laurents, Douglas V.
Venue
Archives of Biochemistry and Biophysics
Publisher
Elsevier BV
Published
2024-06
Volume
756
Pages
109981
ISSN
0003-9861 (ISSN-L)
DOI
10.1016/j.abb.2024.109981
OpenAlex
W4394062884
Cited by
9
References
4
Citations by year
2026: 3 · 2025: 5 · 2024: 1
FWCI
0.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Archives of Biochemistry and Biophysics (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • Ministerio de Ciencia, Innovación y Universidades (MICIN/ AEI / 10.13039/501100011033, MICIN/AEI/10.13039/501100011033/FEDER)
  • Federación Española de Enfermedades Raras
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
polyproline II helix, protein architecture, protein design, hydrogen bonding, protein folding, protein packing, intrinsically disordered regions
MeSH terms
Protein Domains, Protein Conformation, alpha-Helical, Amino Acid Sequence, Glycine, Hydrogen Bonding, Models, Molecular, Peptides, Protein Structure, Secondary, Protein Folding

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