Adhesion mechanism of human β2-glycoprotein I to phospholipids based on its crystal structure
Adhesion mechanism of human β2-glycoprotein I to phospholipids based on its crystal structure
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DOI：
10.1093/emboj/18.19.5166
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发表时间：
1999-10-01
期刊：
影响因子：
11.4
通讯作者：
Gros, P
中科院分区：
文献类型：
--
作者：
Bouma, B;de Groot, PG;Gros, P
人β(2)-糖蛋白I是一种高度糖化的五区质膜黏附蛋白，与凝血和清除循环中的凋亡小体有关。它也是自身免疫性疾病抗磷脂综合征的关键抗原。从人血浆中分离的β(2)-糖蛋白I的晶体结构显示，球状短共识重复结构域呈拉长的鱼钩状排列。正如在结构域1到4中观察到的那样，C-末端第五个结构域的一半强烈偏离标准折叠。这个异常的一半形成了一个特定的磷脂结合部位。一个由14个正电荷残基组成的大片提供了与阴离子磷脂头基的静电相互作用，一个暴露的膜插入环产生了脂层的特异性。观察到的这五个结构域的空间排列表明，蛋白质黏附和膜黏附分别在N和C-末端结构域上进行了功能分割，由糖基化的桥连结构域分开。坐标在蛋白质数据库(登录号：1QUB)中。
Human beta(2)-glycoprotein I is a heavily glycosylated five-domain plasma membrane-adhesion protein, which has been implicated in blood coagulation and clearance of apoptotic bodies from the circulation. It is also the key antigen in the autoimmune disease anti-phospholipid syndrome. The crystal structure of beta(2)-glycoprotein I isolated from human plasma reveals an elongated fishhook-like arrangement of the globular short consensus repeat domains. Half of the C-terminal fifth domain deviates strongly from the standard fold, as observed in domains one to four. This aberrant half forms a specific phospholipid-binding site. A large patch of 14 positively charged residues provides electrostatic interactions with anionic phospholipid headgroups and an exposed membrane-insertion loop yields specificity for lipid layers. The observed spatial arrangement of the five domains suggests a functional partitioning of protein adhesion and membrane adhesion over the Nand C-terminal domains, respectively, separated by glycosylated bridging domains. Coordinates are in the Protein Data Bank (accession No. 1QUB).