A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head
A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head
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DOI：
10.1016/j.str.2004.11.006
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发表时间：
2005-01-01
期刊：
影响因子：
5.7
通讯作者：
Barsukov, IL
中科院分区：
文献类型：
--
作者：
Fillingham, I;Gingras, AR;Barsukov, IL
细胞骨架蛋白踝蛋白在激活整合素并将其与肌动蛋白细胞骨架偶联方面发挥着关键作用。其 N 端球状头与 β 整联蛋白结合，与具有 C 端肌动蛋白结合位点和几个纽蛋白结合位点 (VBS) 的延伸杆相连。杆（含有 VBS）残基 755-889 的 NMR 结构显示为具有左手拓扑的两亲性四螺旋束。对应于VBS的踝蛋白肽结合纽蛋白头；该复合物的X射线晶体结构表明，与纽蛋白相互作用的残基埋藏在talin片段的疏水核心中。 NMR 显示，相互作用涉及 talin 片段的主要结构变化，包括其螺旋之一的展开，使 VBS 能够接触到纽蛋白。有趣的是，talin 755-889 片段结合了不止一个纽蛋白头分子，表明talin 杆可能含有其他尚未识别的 VBS。
The cytoskeletal protein talin plays a key role in activating integrins and in coupling them to the actin cytoskeleton. Its N-terminal globular head, which binds beta integrins, is linked to an extended rod having a C-terminal actin binding site and several vinculin binding sites (VBSs). The NMR structure of residues 755-889 of the rod (containing a VBS) is shown to be an amphipathic four-helix bundle with a left-handed topology. A talin peptide corresponding to the VBS binds the vinculin head; the X-ray crystallographic structure of this complex shows that the residues which interact with vinculin are buried in the hydrophobic core of the talin fragment. NMR shows that the interaction involves a major structural change in the talin fragment, including unfolding of one of its helices, making the VBS accessible to vinculin. Interestingly, the talin 755-889 fragment binds more than one vinculin head molecule, suggesting that the talin rod may contain additional as yet unrecognized VBSs.