Structure and binding mechanism of vascular endothelial cadherin: a divergent classical cadherin.

Structure and binding mechanism of vascular endothelial cadherin: a divergent classical cadherin.
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DOI:
10.1016/j.jmb.2011.01.031
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发表时间:
2011-04-22
影响因子:
5.6
通讯作者:
Shapiro L
Shapiro L
中科院分区:
生物学2区
文献类型:
--
作者:
Brasch J;Harrison OJ;Ahlsen G;Carnally SM;Henderson RM;Honig B;Shapiro L

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血管内皮细胞钙粘蛋白(Vascular endothelial cadherin,VE)是II型经典钙粘蛋白家族中的一个成员,它介导血管内皮细胞的嗜同性粘附。先前对细菌产生的蛋白质的研究表明,VE-钙粘蛋白形成细胞表面三聚体,其在并列细胞之间结合以形成六聚体。在这里,我们报告的研究表明,像其他经典的钙粘蛋白,VE-钙粘蛋白形成粘合剂的反式二聚体之间的单体位于相对的细胞表面上的megalian生产VE-钙粘蛋白胞外域。细菌产生的蛋白质的三聚体似乎是由于缺乏糖基化而产生的假象。我们还提出了2.1nm分辨率的VE-钙粘蛋白EC 1 -2粘附区域的晶体结构,揭示了通过常见的经典钙粘蛋白的链交换机制的同源二聚化。与II型钙粘蛋白一样,链交换结合涉及两个色氨酸锚残基,但粘附界面类似于I型钙粘蛋白,因为VE-钙粘蛋白不形成大的非交换疏水表面。因此,VE-钙粘蛋白是经典钙粘蛋白中的异常值,具有I型和II型亚家族的特征。
Vascular endothelial (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 which bind between apposed cells to form hexamers. Here we report studies of mammalian-produced VE-cadherin ectodomains which suggest 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 2.1Å 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 non-swapped hydrophobic surface. Thus, VE-cadherin is an outlier among classical cadherins, with characteristics of both type I and type II subfamilies.
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