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Structural basis of homo- and heterotrimerization of collagen I

DOI: 10.1038/ncomms14671 DOI Help

Authors: Urvashi Sharma (CNRS - University of Lyon 1) , Loïc Carrique (CNRS - University of Lyon 1) , Sandrine Vadon-le Goff (CNRS - University of Lyon 1) , Natacha Mariano (CNRS - University of Lyon 1) , Rainier-numa Georges (CNRS - University of Lyon 1) , Frederic Delolme (CNRS - University of Lyon 1) , Peppi Koivunen (University of Oulu) , Johanna Myllyharju (University of Oulu) , Catherine Moali (CNRS - University of Lyon 1) , Nushin Aghajari (CNRS - University of Lyon 1) , David J. S. Hulmes (CNRS - University of Lyon 1)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 8

State: Published (Approved)
Published: March 2017
Diamond Proposal Number(s): 9634

Open Access Open Access

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.

Journal Keywords: Proteins; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: B21-High Throughput SAXS

Other Facilities: Swiss Light Source; European Synchrotron Radiation Facility

Added On: 08/05/2017 13:29


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