Roy Anupom, Gauld James W
Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N8S 1C1, Canada.
ACS Omega. 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. eCollection 2022 Nov 8.
Collagen IV networks are an essential component of basement membranes that are important for their structural integrity and thus that of an organism's tissues. Improper functioning of these networks has been associated with several diseases. Cross-links, such as sulfilimine bonds interconnecting NC1 domains, are critical for forming and mechanically stabilizing these collagen IV networks. More specifically, the sulfilimine cross-links form between methionine (Met93) and lysine/hydroxylsine (Lys211/Hyl211) residues of NC1 domains. Therefore, the dynamic nature of the sulfilimine bond in collagen IV is crucial for network formation. To understand the dynamic nature of a neutral and protonated sulfilimine bond in collagen IV, we performed molecular dynamics (MD) simulations on four sulfilimine cross-linked systems (i.e., S-N, S-NH , S-N, and S-NH ) of collagen IV. The MD results showed that the neutral S-N system has the smallest protein backbone and showed the cross-linked residues' RMSD value. The conformational change analyses showed that the conformations of the sulfilimine cross-linked residues take on a U-shape for the S-N and S-HN systems, whereas the conformations of the sulfilimine cross-linked residues are more open for the S-N, and S-NH systems. Protonation is a crucial biochemical process to stabilize the protein structure or the biological cross-links. Furthermore, the protonation of the sulfilimine bond could potentially influence hydrogen bond interaction with near amino acid residues, and according to water distribution analyses, the sulfilimine bond can potentially exist in one or more protonation states.
IV型胶原蛋白网络是基底膜的重要组成部分，对其结构完整性以及生物体组织的结构完整性至关重要。这些网络功能异常与多种疾病相关。交联键，如连接NC1结构域的亚磺酰亚胺键，对于形成并机械稳定这些IV型胶原蛋白网络至关重要。更具体地说，亚磺酰亚胺交联键在NC1结构域的甲硫氨酸（Met93）和赖氨酸/羟赖氨酸（Lys211/Hyl211）残基之间形成。因此，IV型胶原蛋白中亚磺酰亚胺键的动态性质对于网络形成至关重要。为了解IV型胶原蛋白中中性和质子化亚磺酰亚胺键的动态性质，我们对IV型胶原蛋白的四个亚磺酰亚胺交联系统（即S-N、S-NH 、S-N和S-NH ）进行了分子动力学（MD）模拟。MD结果表明，中性S-N系统具有最小的蛋白质主链，并显示出交联残基的均方根偏差（RMSD）值。构象变化分析表明，对于S-N和S-HN 系统，亚磺酰亚胺交联残基的构象呈U形，而对于S-N和S-NH 系统，亚磺酰亚胺交联残基的构象更为开放。质子化是稳定蛋白质结构或生物交联的关键生化过程。此外，亚磺酰亚胺键的质子化可能会影响与附近氨基酸残基的氢键相互作用，并且根据水分布分析，亚磺酰亚胺键可能以一种或多种质子化状态存在。
