School of Chemistry Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, 4001 Australia.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Glycobiology. 2020 Sep 28;30(10):830-843. doi: 10.1093/glycob/cwaa026.
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.
胶原经历多种类型的翻译后修饰（PTMs），包括细胞内修饰和细胞外修饰。在这些 PTM 中，羟赖氨酸（Hyl）的糖基化最为复杂。实验研究表明，一旦胶原三螺旋形成，这种 PTM 就会停止，并且 Hyl-O-糖基化调节胶原原纤维的形成。然而，这些现象的潜在原子水平机制尚不清楚。在这项研究中，我们首先适应了 Hyl 和碳水化合物之间的 O 键的力场参数，然后通过在含有和不含有 Hyl 糖基化的胶原分子片段的明胶溶剂中进行全面的分子动力学模拟，研究了 Hyl-O-糖基化对 I 型胶原分子结构的影响。数据分析表明：（i）Hyl 糖基化后胶原三螺旋仍保持三螺旋结构；（ii）Hyl 糖基化调节肽骨架构象及其附近的溶剂环境；（iii）连接的糖被排列成使得它们的亲水面很好地暴露在溶剂中，而它们的疏水面指向胶原的疏水部分。适应 Hyl 和碳水化合物之间的 O 键的力场参数将有助于未来具有 Hyl-O-糖基化的蛋白质的计算研究。此外，这项工作首次在原子水平上展示了 Hyl-O-糖基化对人 I 型胶原结构的详细影响，这可能为胶原类生物材料的设计和制造以及胶原相关疾病的生物医学治疗的发展提供见解。
