Crystal structure of human vinculin
Crystal structure of human vinculin
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DOI：
10.1016/j.str.2004.05.009
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发表时间：
2004-07-01
期刊：
影响因子：
5.7
通讯作者：
Izard, T
中科院分区：
文献类型：
--
作者：
Borgon, RA;Vonrhein, C;Izard, T
在肌动蛋白细胞骨架的细胞基质和细胞连接的形成后，由黏着斑蛋白协调。巨噬细胞蛋白与大量的细胞骨架和信号蛋白相关联，并且这种灵活性被认为有助于粘附复合物的快速解离和重新缔合。黏着斑蛋白的头部（Vh）和尾部（Vt）结构域之间的分子内相互作用限制了其他粘附蛋白的结合位点。虽然Vh和Vt结构域的晶体结构是已知的，但这些结构域占整个蛋白质的不到一半，并且被结构和功能未知的大中心区域分开。在这里，我们报告的晶体结构的人全长纽蛋白到2.85埃。分辨率在其静止状态下，黏着斑蛋白是通过Vh-Vt相互作用保持在一起的α-螺旋束的松散堆积的集合。这三个新的有序的α-螺旋束结构域在其结构上与Vh（Vh 2和Vh 3）或Vt（Vt 2）相似，并且它们的松散包装提供了必要的灵活性，使得黏着斑蛋白在细胞粘附位点与其各种蛋白质伴侣相互作用。
Alterations in the actin cytoskeleton following the formation of cell-matrix and cell-cell junctions are orchestrated by vinculin. Vinculin associates with a large number of cytoskeletal and signaling proteins, and this flexibility is thought to contribute to rapid dissociation and reassociations of adhesion complexes. Intramolecular interactions between vinculin's head (Vh) and tail (Vt) domains limit access of its binding sites for other adhesion proteins. While the crystal structures of the Vh and Vt domains are known, these domains represent less than half of the entire protein and are separated by a large central region of unknown structure and function. Here we report the crystal structure of human full-length vinculin to 2.85 Angstrom. resolution. In its resting state, vinculin is a loosely packed collection of alpha-helical bundles held together by Vh-Vt interactions. The three new well ordered alpha-helical bundle domains are similar in their structure to either Vh (Vh2 and Vh3) or to Vt (Vt2) and their loose packing provides the necessary flexibility that allows vinculin to interact with its various protein partners at sites of cell adhesion.