Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, New York, NY 10032, USA.
J Mol Biol. 2011 Apr 22;408(1):57-73. doi: 10.1016/j.jmb.2011.01.031. Epub 2011 Jan 24.
Vascular endothelial cadherin (VE-cadherin), a divergent member of the type II classical cadherin family of cell adhesion proteins, mediates homophilic adhesion in the vascular endothelium. Previous investigations with a bacterially produced protein suggested that VE-cadherin forms cell surface trimers that bind between apposed cells to form hexamers. Here we report studies of mammalian-produced VE-cadherin ectodomains suggesting that, like other classical cadherins, VE-cadherin forms adhesive trans dimers between monomers located on opposing cell surfaces. Trimerization of the bacterially produced protein appears to be an artifact that arises from a lack of glycosylation. We also present the 2.1-Å-resolution crystal structure of the VE-cadherin EC1-2 adhesive region, which reveals homodimerization via the strand-swap mechanism common to classical cadherins. In common with type II cadherins, strand-swap binding involves two tryptophan anchor residues, but the adhesive interface resembles type I cadherins in that VE-cadherin does not form a large nonswapped hydrophobic surface. Thus, VE-cadherin is an outlier among classical cadherins, with characteristics of both type I and type II subfamilies.
血管内皮钙黏蛋白（VE-cadherin）是细胞黏附蛋白的 II 型经典钙黏蛋白家族中的一个独特成员，介导血管内皮中的同质黏附。先前使用细菌产生的蛋白质进行的研究表明，VE-cadherin 形成细胞表面三聚体，这些三聚体在相邻细胞之间结合形成六聚体。在这里，我们报告了对哺乳动物产生的 VE-cadherin 外域的研究，表明与其他经典钙黏蛋白一样，VE-cadherin 在位于相对细胞表面的单体之间形成具有粘附性的跨二聚体。细菌产生的蛋白质的三聚化似乎是由于缺乏糖基化而产生的一种假象。我们还展示了 VE-cadherin EC1-2 黏附区的 2.1-Å 分辨率晶体结构，该结构揭示了通过经典钙黏蛋白共有的链交换机制发生同源二聚化。与 II 型钙黏蛋白一样，链交换结合涉及两个色氨酸锚定残基，但黏附界面与 I 型钙黏蛋白相似，因为 VE-cadherin 不会形成大的非交换疏水面。因此，VE-cadherin 是经典钙黏蛋白中的一个异类，具有 I 型和 II 型亚家族的特征。
