Laboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Nat Commun. 2021 Jun 29;12(1):4012. doi: 10.1038/s41467-021-24184-8.
Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we report the structures of the prototypic laminin receptor α6β1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin γ1 chain C-terminal portion providing focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin β1 subunit and Asn189 of integrin α6 subunit. Laminin α5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the β-propeller domain of α6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture.
整合素受体对层粘连蛋白的识别是上皮细胞黏附基底膜的核心，但这种分子相互作用的结构背景仍不清楚。在这里，我们通过晶体学和 cryo-电子显微镜分别报告了原型层粘连蛋白受体α6β1 整合素及其与三链层粘连蛋白-511 片段复合物的结构。层粘连蛋白-整合素界面由位于所有五个亚基上的几个结合位点组成，其中层粘连蛋白 γ1 链 C 末端部分通过两个羧酸盐锚定点提供焦点相互作用，以桥接整合素β1 亚基的金属离子依赖性黏附位点和整合素α6 亚基的 Asn189。层粘连蛋白α5 链也通过与α6 的β-推进器结构域上的大表面进行静电相互作用来增加亲和力和特异性，其中一部分包含一个选择性剪接的 X1 区域。与该区域相对应的推进器片表现出异常高的迁移率，表明其在配体捕获中具有独特的作用。
