Structural basis of homo- and heterotrimerization of collagen I
Sharma, Urvashi; Carrique, Loïc; Vadon-Le Goff, Sandrine; Mariano, Natacha; Georges, Rainier-Numa; Delolme, Frederic; Koivunen, Peppi; Myllyharju, Johanna; Moali, Catherine; Aghajari, Nushin; Hulmes, David J. S. (2017-03-10)
Sharma, U. et al. Structural basis of homo- and heterotrimerization of collagen I. Nat. Commun. 8, 14671 doi: 10.1038/ncomms14671 (2017).
©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/
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe201703275838
Tiivistelmä
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.
Kokoelmat
- Avoin saatavuus [29905]
