Three-dimensional structure of vinculin bound to actin filaments
Three-dimensional structure of vinculin bound to actin filaments
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DOI：
10.1016/j.molcel.2005.11.020
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发表时间：
2006-01-20
期刊：
影响因子：
16
通讯作者：
Hanein, D
中科院分区：
文献类型：
--
作者：
Janssen, MEW;Kim, E;Hanein, D
肌动蛋白通过在肌动蛋白细胞骨架和跨膜受体整合素和钙粘蛋白之间提供连接而在细胞粘附和迁移中起关键作用。我们使用电子显微镜，计算对接，和生物化学的组合，以提供一个原子模型的黏着斑蛋白高结合肌动蛋白丝。黏着斑蛋白尾部肌动蛋白结合位点包括两个不同的区域。其中一个区域暴露在黏着斑蛋白的全长自抑制构象中，而第二个位点被黏着斑蛋白的N-末端结构域空间封闭。自抑制全长黏着斑蛋白结构中F-肌动蛋白结合位点的部分可及性表明F-肌动蛋白可以作为与其他结合伴侣（如α-连环蛋白或talin）组合输入框架的一部分，以诱导黏着斑蛋白头高解离，从而促进黏着斑蛋白活化。此外，结合到F-肌动蛋白增强了黏着斑蛋白尾部的局部重排，这反过来又促进黏着斑蛋白二聚化，从而形成肌动蛋白束。
Vinculin plays a pivotal role in cell adhesion and migration by providing the link between the actin cytoskeleton and the transmembrane receptors, integrin and cadherin. We used a combination of electron microscopy, computational docking, and biochemistry to provide an atomic model of how the vinculin tall binds actin filaments. The vinculin tail actin binding site comprises two distinct regions. One of these regions is exposed in the full-length autoinhibited conformation of vinculin, whereas the second site is sterically occluded by vinculin's N-terminal domain. The partial accessibility of the F-actin binding site in the autoinhibited full-length vinculin structure suggests that F-actin can act as part of a combinatorial input framework with other binding partners such as alpha-catenin or talin to induce vinculin head-tall dissociation, thus promoting vinculin activation. Furthermore, binding to F-actin potentiates a local rearrangement in the vinculin tail that in turn promotes vinculin dimerization and, hence, formation of actin bundles.