Functional analysis of the structural basis of homophilic cadherin adhesion.
Functional analysis of the structural basis of homophilic cadherin adhesion.
复制标题
同亲钙粘蛋白粘附结构基础的功能分析。
DOI：
10.1016/s0006-3495(03)75129-7
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Leckband,D
中科院分区：
文献类型：
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作者：
Zhu,B;Chappuis-Flament,S;Wong,E;Jensen,IE;Gumbiner,BM;Leckband,D
许多细胞表面粘附蛋白的结构包含结构相似结构域的多个串联重复。在许多情况下，这种结构的功能意义是未知的，有几种情况下，证据表明，个别领域参与粘附一直是矛盾的。特别地，粘附糖蛋白钙粘蛋白的胞外区由五个串联排列的结构域组成。一种提出的机制假设，粘附只涉及最外层结构域之间的相互作用。然而，随后的调查产生了几个相互竞争的模型。在这里，我们描述了直接测量的距离依赖性的相互作用之间的潜力缺乏不同的结构域的钙粘蛋白突变体。通过量化的绝对距离，在反对钙粘蛋白片段结合和量化的变化，导致从个别域的缺失的相互作用的潜力，我们表明，两个域参与嗜同性钙粘蛋白结合。这一发现与目前认为钙粘蛋白通过蛋白质表面上的单个独特位点结合的观点形成对比。涉及多个结构域的相互作用产生的潜力产生了一种新的，模块化的结合机制，其中相对的钙粘蛋白胞外域可以坚持在任何三个反平行对齐。
The structures of many cell surface adhesion proteins comprise multiple tandem repeats of structurally similar domains. In many cases, the functional significance of this architecture is unknown, and there are several cases in which evidence for individual domain involvement in adhesion has been contradictory. In particular, the extracellular region of the adhesion glycoprotein cadherin consists of five tandemly arranged domains. One proposed mechanism postulated that adhesion involves onlytransinteractions between the outermost domains. However, subsequent investigations have generated several competing models. Here we describe direct measurements of the distance-dependent interaction potentials between cadherin mutants lacking different domains. By quantifying both the absolute distances at which opposed cadherin fragments bind and the quantized changes in the interaction potentials that result from deletions of individual domains, we demonstrate that two domains participate in homophilic cadherin binding. This finding contrasts with the current view that cadherins bind via a single, unique site on the protein surface. The potentials that result from interactions involving multiple domains generate a novel, modular binding mechanism in which opposed cadherin ectodomains can adhere in any of three antiparallel alignments.