Crystal structure of the vinculin tail suggests a pathway for activation
Crystal structure of the vinculin tail suggests a pathway for activation
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DOI：
10.1016/s0092-8674(00)81549-4
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发表时间：
1999-12-10
期刊：
影响因子：
64.5
通讯作者：
Liddington, RC
中科院分区：
文献类型：
--
作者：
Bakolitsa, C;de Pereda, JM;Liddington, RC
肌动蛋白在肌动蛋白细胞骨架的组装中起着动态作用。其头部和尾部结构域之间的强相互作用调节与其他细胞骨架组分的结合被酸性磷脂破坏。在这里，我们提出了黏着斑蛋白尾部的晶体结构，残基879-1066。五个两亲性螺旋形成类似于可交换载脂蛋白的反平行束。C-末端臂缠绕在束的基部上，并作为疏水发夹出现，其被邻近N末端的碱性残基环包围。我们表明，C-末端臂是必需的结合酸性磷脂，但不是肌动蛋白，结合任何配体诱导的构象变化，可能代表激活的第一步。
Vinculin plays a dynamic role in the assembly of the actin cytoskeleton. A strong interaction between its head and tail domains that regulates binding to other cytoskeletal components is disrupted by acidic phospholipids. Here, we present the crystal structure of the vinculin tail, residues 879-1066. Five amphipathic helices form an antiparallel bundle that resembles exchangeable apolipoproteins. A C-terminal arm wraps across the base of the bundle and emerges as a hydrophobic hairpin surrounded by a collar of basic residues, adjacent to the N terminus. We show that the C-terminal arm is required for binding to acidic phospholipids but not to actin, and that binding either ligand induces conformational changes that may represent the first step in activation.