University of Oulu

Sharma, U. et al. Structural basis of homo- and hetero- trimerization of collagen I. Nat. Commun. 8, 14671 doi: 10.1038/ncomms14671 (2017).

Structural basis of homo- and heterotrimerization of collagen I

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Author: Sharma, Urvashi1; Carrique, Loïc1; Vadon-Le Goff, Sandrine2;
Organizations: 1Molecular Microbiology and Structural Biochemistry Unit, UMR 5086 CNRS - University of Lyon 1, 7 passage du Vercors, F-69367 Lyon, France
2Tissue Biology and Therapeutic Engineering Unit, UMR 5305 CNRS - University of Lyon 1, 7 passage du Vercors, F-69367 Lyon, France
3SFR Biosciences - Protein Science Facility, University of Lyon 1, Ecole Normale Supérieure de Lyon, INSERM US8, CNRS UMS 3444, 50 Avenue Tony Garnier, F-69366 Lyon, France
4Oulu Center for Cell-Matrix Research, Biocenter Oulu, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
5Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5000, FI-90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe201703275838
Language: English
Published: Nature Publishing Group, 2017
Publish Date: 2017-03-27
Description:

Abstract

Fibrillar collagen molecules are synthesized as precursors, procollagens, with large propeptide extensions. While a homotrimeric form (three α1 chains) has been reported in embryonic tissues as well as in diseases (cancer, fibrosis, genetic disorders), collagen type I usually occurs as a heterotrimer (two α1 chains and one α2 chain). Inside the cell, the role of the C-terminal propeptides is to gather together the correct combination of three α chains during molecular assembly, but how this occurs for different forms of the same collagen type is so far unknown. Here, by structural and mutagenic analysis, we identify key amino acid residues in the α1 and α2 C-propeptides that determine homo- and heterotrimerization. A naturally occurring mutation in one of these alters the homo/heterotrimer balance. These results show how the C-propeptide of the α2 chain has specifically evolved to permit the appearance of heterotrimeric collagen I, the major extracellular building block among the metazoa.
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Series: Nature communications
ISSN: 2041-1723
ISSN-E: 2041-1723
ISSN-L: 2041-1723
Volume: 8
Pages: 1 - 10
Article number: 14671
DOI: 10.1038/ncomms14671
OADOI: https://oadoi.org/10.1038/ncomms14671
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Subjects:
Funding: This research was funded by the French National Research Agency (project ‘TOLLREG’), the European Community’s Seventh Framework Programme (FP7/2007–2013; BioStruct-X, grant agreement N°283570), the CNRS, the Université Claude Bernard Lyon 1 and the Région Rhone-Alpes (Ph.D. scholarship to L.C.).
EU Grant Number: (283570) BIOSTRUCT-X - Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities
Copyright information: ©The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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