Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members
Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members
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DOI：
10.1073/pnas.1006284107
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发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Mueller, Ulrich
中科院分区：
文献类型：
--
作者：
Elledge, Heather M.;Kazmierczak, Piotr;Mueller, Ulrich
钙粘蛋白超家族编码100多种受体，在组织发育和体内平衡中具有不同的功能。经典钙粘蛋白通过依赖于其N-末端细胞外钙粘蛋白（EC）结构域的结合相互作用介导粘附，所述结构域交换N-末端β链。序列比对表明，链交换结合模式是不常用的功能不同的钙粘蛋白。在这里，我们已经确定了钙粘蛋白23（CDH 23）的EC 1-EC2结构域的结构，该结构域与原钙粘蛋白15（PCDH 15）结合形成机械感觉毛细胞的尖端连接。与经典钙粘蛋白不同，CDH 23 N末端含有结合Ca 2+的极性氨基酸。PCDH 15的N末端也含有极性氨基酸。CDH 23和PCDH 15的EC 1内的极性氨基酸的突变消除了两种钙粘蛋白之间的相互作用。PCDH 21和PCDH 24含有类似的带电N末端，这表明钙粘蛋白的一个子集共享一个共同的相互作用机制，不同于经典钙粘蛋白的链交换结合模式。
The cadherin superfamily encodes more than 100 receptors with diverse functions in tissue development and homeostasis. Classical cadherins mediate adhesion by binding interactions that depend on their N-terminal extracellular cadherin (EC) domains, which swap N-terminal beta-strands. Sequence alignments suggest that the strand-swap binding mode is not commonly used by functionally divergent cadherins. Here, we have determined the structure of the EC1-EC2 domains of cadherin 23 (CDH23), which binds to protocadherin 15 (PCDH15) to form tip links of mechanosensory hair cells. Unlike classical cadherins, the CDH23 N terminus contains polar amino acids that bind Ca2+. The N terminus of PCDH15 also contains polar amino acids. Mutations in polar amino acids within EC1 of CDH23 and PCDH15 abolish interaction between the two cadherins. PCDH21 and PCDH24 contain similarly charged N termini, suggesting that a subset of cadherins share a common interaction mechanism that differs from the strand-swap binding mode of classical cadherins.