Deciphering the folding code of collagens

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• dc.contributor.author Malcor, Jean-Daniel
• dc.contributor.author Ferruz Capapey, Noelia, 1988-
• dc.contributor.author Romero-Romero, Sergio
• dc.contributor.author Dhingra, Surbhi
• dc.contributor.author Sagar, Vamika
• dc.contributor.author Jalan, Abhishek A.
• dc.date.accessioned 2025-05-14T06:02:49Z
• dc.date.available 2025-05-14T06:02:49Z
• dc.date.issued 2025
• dc.description.abstract Collagen proteins contain a characteristic structural motif called a triple helix. During the self-assembly of this motif, three polypeptides form a folding nucleus at the C-termini and then propagate towards the N-termini like a zip-chain. While polypeptides from human collagens contain up to a 1000 amino acids, those found in bacteria can contain up to 6000 amino acids. Additionally, the collagen polypeptides are also frequently interrupted by non-helical sequences that disrupt folding and reduce stability. Given the length of polypeptides and the disruptive interruptions, compensating mechanisms that stabilize against local unfolding during propagation and offset the entropic cost of folding are not fully understood. Here, we show that the information for the correct folding of collagen triple helices is encoded in their sequence as interchain electrostatic interactions, which likely act as molecular clamps that prevent local unfolding. In the case of humans, disrupting these electrostatic interactions is associated with severe to lethal diseases.
• dc.description.sponsorship Part of the work was funded by the Newton International Alumni Funding (2018-2023) awarded to A.A.J jointly by the Royal Society, the British Academy, and the Academy of Medical Sciences. J.D.M was partly funded by the French National Agency (CARTEGRIN ANR21-CE19-0017). S.R.R. was funded by a fellowship from the Alexander von Humboldt and Bayer Science & Education Foundations, NF was funded by the ERC Consolidator Grant 647548 and SD was funded by VolkswagenStiftung Grant 94747. The authors would like to thank Prof Birte Höcker for access to the DSC instruments. The authors gratefully acknowledge the scientific support and HPC resources provided by the Erlangen National High-Performance Computing Center (NHR@FAU) of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) under the NHR project b114cb (UID 210235). NHR funding is provided by federal and Bavarian state authorities. NHR@FAU hardware is partially funded by the German Research Foundation (DFG) – 440719683. We also thank Prof Thomas Scheibel for laboratory resources for executing part of this project. The authors specially thank Prof Richard Farndale for insightful discussion and help with the peptide synthesis.
• dc.format.mimetype application/pdf
• dc.identifier.citation Malcor JD, Ferruz N, Romero-Romero S, Dhingra S, Sagar V, Jalan AA. Deciphering the folding code of collagens. Nat Commun. 2025 Mar 19;16(1):2702. DOI: 10.1038/s41467-024-54046-y
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-54046-y
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/70386
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2025 Mar 19;16(1):2702
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/647548
• dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Biophysics
• dc.subject.keyword Protein folding
• dc.subject.keyword Proteins
• dc.title Deciphering the folding code of collagens
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion