Structure of the cadherin-related neuronal receptor/protocadherin-α first extracellular cadherin domain reveals diversity across cadherin families
Structure of the cadherin-related neuronal receptor/protocadherin-α first extracellular cadherin domain reveals diversity across cadherin families
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DOI：
10.1074/jbc.m603298200
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发表时间：
2006-11-03
影响因子：
4.8
通讯作者：
Ikegami, Takahisa
中科院分区：
文献类型：
--
作者：
Morishita, Hirofumi;Umitsu, Masataka;Ikegami, Takahisa
最近的基因组测序的爆炸揭示了钙粘蛋白超家族的巨大多样性。在超家族中，主要在神经系统中表达的原钙粘素构成最大的亚组。然而，只有经典的钙粘蛋白的结构是已知的。因此，为了拓宽我们对钙粘蛋白超家族粘附谱的理解，我们确定了钙粘蛋白相关神经元受体/原钙粘蛋白-α 4的N-末端第一胞外钙粘蛋白结构域的结构。在经典钙粘蛋白中没有发现嗜同性粘附所必需的疏水口袋，并且通过交换原钙粘蛋白和经典钙粘蛋白的第一胞外钙粘蛋白结构域来支持该结构域的功能意义。此外，主要在环区域观察到潜在的关键变化。这些包括原钙粘蛋白特异性二硫键结合的Cys-X-5-Cys基序，其显示出Ca 2+诱导的化学位移，以及RGD基序，其已被认为通过β 1整合素的活性形式参与嗜异性细胞粘附。我们的研究结果表明，粘附剧目的钙粘蛋白超家族是远远超过将通过单独研究经典的钙粘蛋白预测的分歧。
The recent explosion in genome sequencing has revealed the great diversity of the cadherin superfamily. Within the superfamily, protocadherins, which are expressed mainly in the nervous system, constitute the largest subgroup. Nevertheless, the structures of only the classical cadherins are known. Thus, to broaden our understanding of the adhesion repertoire of the cadherin superfamily, we determined the structure of the N-terminal first extracellular cadherin domain of the cadherin-related neuronal receptor/protocadherin-alpha 4. The hydrophobic pocket essential for homophilic adhesiveness in the classical cadherins was not found, and the functional significance of this structural domain was supported by exchanging the first extracellular cadherin domains of protocadherin and classical cadherin. Moreover, potentially crucial variations were observed mainly in the loop regions. These included the protocadherin-specific disulfide-bonded Cys-X-5-Cys motif, which showed Ca2+-induced chemical shifts, and the RGD motif, which has been suggested to be involved in heterophilic cell adhesion via the active form of beta 1 integrin. Our findings reveal that the adhesion repertoire of the cadherin superfamily is far more divergent than would be predicted by studying the classical cadherins alone.