A specific interface between integrin transmembrane helices and affinity for ligand.
A specific interface between integrin transmembrane helices and affinity for ligand.
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DOI：
10.1371/journal.pbio.0020153
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发表时间：
2004-06
期刊：
影响因子：
9.8
通讯作者：
Takagi J
中科院分区：
文献类型：
--
作者：
Luo BH;Springer TA;Takagi J
整合素的细胞外和细胞内结构域之间跨质膜的构象通讯开始由两个结构域的结构工作来定义。然而，α和β亚基跨膜结构域的作用以及通过这些结构域的信号传递的性质一直难以捉摸。整合素αIIβ和β3跨膜结构域的外表面部分的二硫键扫描揭示了静息受体中的特异性异源二聚化界面。通过模拟生理性由内而外激活的α亚基的胞质突变激活受体后，该界面丢失而不是重排，表明胞外结构域的激活与跨膜螺旋的横向分离之间存在联系。引入二硫桥以防止或逆转分离消除了细胞质突变的激活作用，证实跨膜结构域分离而不是铰链或活塞样运动作为整联蛋白跨膜信号传导的机制。整合素受体通过改变其胞内和胞外结构域的构象来介导细胞-基质相互作用，这一过程由跨膜螺旋的侧向分离介导
Conformational communication across the plasma membrane between the extracellular and intracellular domains of integrins is beginning to be defined by structural work on both domains. However, the role of the α and β subunit transmembrane domains and the nature of signal transmission through these domains have been elusive. Disulfide bond scanning of the exofacial portions of the integrin αIIβ and β3 transmembrane domains reveals a specific heterodimerization interface in the resting receptor. This interface is lost rather than rearranged upon activation of the receptor by cytoplasmic mutations of the α subunit that mimic physiologic inside-out activation, demonstrating a link between activation of the extracellular domain and lateral separation of transmembrane helices. Introduction of disulfide bridges to prevent or reverse separation abolishes the activating effect of cytoplasmic mutations, confirming transmembrane domain separation but not hinging or piston-like motions as the mechanism of transmembrane signaling by integrins. Integrin receptors mediate cell-matrix interactions by altering the conformation of their intra- and extra- cellular domains, a process mediated by lateral separation of the transmembrane helices
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