Effect of hydroxylysine-O-glycosylation on the structure of type I collagen molecule: A computational study.

Autor:	Tang M; School of Chemistry Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, 4001 Australia., Wang X; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA., Gandhi NS; School of Mathematical Sciences, Queensland University of Technology, Brisbane 4001, Australia., Foley BL; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA., Burrage K; School of Mathematical Sciences, Queensland University of Technology, Brisbane 4001, Australia.; ARC Centre of Excellence for Mathematical and Statistical Frontiers, Queensland University of Technology, Brisbane 4001, Australia., Woods RJ; Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA., Gu Y; School of Chemistry Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, 4001 Australia.
Jazyk:	angličtina
Zdroj:	Glycobiology [Glycobiology] 2020 Sep 28; Vol. 30 (10), pp. 830-843.
DOI:	10.1093/glycob/cwaa026
Abstrakt:	Collagen undergoes many types of post-translational modifications (PTMs), including intracellular modifications and extracellular modifications. Among these PTMs, glycosylation of hydroxylysine (Hyl) is the most complicated. Experimental studies demonstrated that this PTM ceases once the collagen triple helix is formed and that Hyl-O-glycosylation modulates collagen fibrillogenesis. However, the underlying atomic-level mechanisms of these phenomena remain unclear. In this study, we first adapted the force field parameters for O-linkages between Hyl and carbohydrates and then investigated the influence of Hyl-O-glycosylation on the structure of type I collagen molecule, by performing comprehensive molecular dynamic simulations in explicit solvent of collagen molecule segment with and without the glycosylation of Hyl. Data analysis demonstrated that (i) collagen triple helices remain in a triple-helical structure upon glycosylation of Hyl; (ii) glycosylation of Hyl modulates the peptide backbone conformation and their solvation environment in the vicinity and (iii) the attached sugars are arranged such that their hydrophilic faces are well exposed to the solvent, while their hydrophobic faces point towards the hydrophobic portions of collagen. The adapted force field parameters for O-linkages between Hyl and carbohydrates will aid future computational studies on proteins with Hyl-O-glycosylation. In addition, this work, for the first time, presents the detailed effect of Hyl-O-glycosylation on the structure of human type I collagen at the atomic level, which may provide insights into the design and manufacture of collagenous biomaterials and the development of biomedical therapies for collagen-related diseases. (© Crown copyright 2020.)
Databáze:	MEDLINE
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