Structural basis for amplifying vinculin activation by talin
Structural basis for amplifying vinculin activation by talin
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DOI：
10.1074/jbc.m403076200
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发表时间：
2004-06-25
影响因子：
4.8
通讯作者：
Vonrhein, C
中科院分区：
文献类型：
--
作者：
Izard, T;Vonrhein, C
塔林蛋白与黏着斑蛋白的相互作用对于局灶性粘连是必不可少的。奇怪的是，talin包含三个非连续的黏着斑蛋白结合位点（VBS），可以单独结合到黏着斑蛋白头（Vh）域。在这里，我们报告的晶体结构的人VH。VBS 1复合体，Vh . VBS 2的结构，和生化研究表明，所有的塔林VBSs激活黏着斑蛋白通过挑起的Vh结构域，取代黏着斑蛋白尾（Vt）域的螺旋束转换。因此，螺旋束转换是talin-vinculin相互作用中结构保守的反应。此外，塔林VBSs结合到Vh在一个相互排斥的方式，但不同的亲和力Vh和他们的能力，取代Vt，这表明这些相互作用的强度可能会导致信号转导结果的差异。这些发现支持了这样一个模型，即塔林蛋白结合并激活多个黏着斑蛋白分子，以引起肌动蛋白细胞骨架的快速重组。
Talin interactions with vinculin are essential for focal adhesions. Curiously, talin contains three noncontiguous vinculin binding sites (VBS) that can bind individually to the vinculin head (Vh) domain. Here we report the crystal structure of the human Vh . VBS1 complex, a validated model of the Vh . VBS2 structure, and biochemical studies that demonstrate that all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain. Thus, helical bundle conversion is a structurally conserved response in talin-vinculin interactions. Furthermore, talin VBSs bind to Vh in a mutually exclusive manner but do differ in their affinity for Vh and in their ability to displace Vt, suggesting that the strengths of these interactions could lead to differences in signaling outcome. These findings support a model in which talin binds to and activates multiple vinculin molecules to provoke rapid reorganization of the actin cytoskeleton.