Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle
Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle
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DOI：
10.1038/sj.emboj.7600285
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发表时间：
2004-08-04
期刊：
影响因子：
11.4
通讯作者：
Emsley, J
中科院分区：
文献类型：
--
作者：
Papagrigoriou, E;Gingras, AR;Emsley, J
细胞骨架蛋白talin和黏着斑蛋白之间的相互作用在整合素介导的细胞粘附和迁移中起着关键作用。我们已经确定了两个域的晶体结构从塔林杆跨越残基482-789。Talin 482-655含有一个黏着斑蛋白结合位点（VBS），折叠成一个五螺旋束，而Talin 656-789是一个四螺旋束。我们表明，VBS是由一个疏水表面跨越5个转弯的螺旋4。来自VBS的所有关键侧链被掩埋并有助于塔林482-655折叠的疏水核心。我们证明，塔林482-655五螺旋束代表一个非活性构象，和突变，破坏疏水核心或删除螺旋5是必需的，以诱导一个活跃的构象，其中VBS暴露。我们还报告了与活化形式塔林复合的N末端粘着斑头部结构域的晶体结构。塔林蛋白中VBS的激活和黏着斑蛋白的募集可能支持小整合素/塔林蛋白复合物成熟为更稳定的粘连。
The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. We have determined the crystal structures of two domains from the talin rod spanning residues 482-789. Talin 482-655, which contains a vinculin-binding site (VBS), folds into a five-helix bundle whereas talin 656-789 is a four-helix bundle. We show that the VBS is composed of a hydrophobic surface spanning five turns of helix 4. All the key side chains from the VBS are buried and contribute to the hydrophobic core of the talin 482-655 fold. We demonstrate that the talin 482-655 five-helix bundle represents an inactive conformation, and mutations that disrupt the hydrophobic core or deletion of helix 5 are required to induce an active conformation in which the VBS is exposed. We also report the crystal structure of the N-terminal vinculin head domain in complex with an activated form of talin. Activation of the VBS in talin and the recruitment of vinculin may support the maturation of small integrin/talin complexes into more stable adhesions.