Borgon Robert A, Vonrhein Clemens, Bricogne Gerard, Bois Philippe R J, Izard Tina
Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105, USA.
Structure. 2004 Jul;12(7):1189-97. doi: 10.1016/j.str.2004.05.009. Epub 2004 Jun 3.
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 A 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.
纽蛋白协调细胞与基质及细胞与细胞间连接形成后肌动蛋白细胞骨架的改变。纽蛋白与大量细胞骨架和信号蛋白相关联，这种灵活性被认为有助于黏附复合体的快速解离和重新结合。纽蛋白头部（Vh）和尾部（Vt）结构域之间的分子内相互作用限制了其与其他黏附蛋白结合位点的可及性。虽然Vh和Vt结构域的晶体结构已知，但这些结构域占整个蛋白质不到一半，且被一个结构和功能未知的大中央区域隔开。在此，我们报告了分辨率为2.85 Å的人全长纽蛋白的晶体结构。在其静止状态下，纽蛋白是由Vh-Vt相互作用维系在一起的α-螺旋束的松散集合。三个新的排列有序的α-螺旋束结构域在结构上与Vh（Vh2和Vh3）或Vt（Vt2）相似，它们的松散排列提供了必要的灵活性，使纽蛋白能够在细胞黏附位点与各种蛋白质伙伴相互作用。
