The Structure of the talin head reveals a novel extended conformation of the FERM domain.
The Structure of the talin head reveals a novel extended conformation of the FERM domain.
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DOI：
10.1016/j.str.2010.07.011
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发表时间：
2010-10-13
期刊：
影响因子：
--
通讯作者：
Barsukov IL
中科院分区：
文献类型：
--
作者：
Elliott PR;Goult BT;Kopp PM;Bate N;Grossmann JG;Roberts GC;Critchley DR;Barsukov IL
FERM结构域存在于不同的信号蛋白超家族和膜界面的衔接蛋白中。它们通常由三个单独折叠的结构域（F1, F2, F3）组成紧凑的三叶草结构。本文报道的整合素相关细胞骨架蛋白talin的n端头部的晶体结构揭示了一个具有线性结构域排列的新型FERM结构域，以及一个与F1堆积的额外结构域F0。虽然F3结合β-整合素尾部，但F1和F2中的基本残基是膜结合和整合素激活所必需的。我们发现这些相同的残基也是细胞扩散和细胞内黏附聚集所必需的。我们认为，talin头部的延伸构象允许同时通过F3与整合素结合，并通过分布在talin头部表面的碱基残基与PtdIns(4,5) p2富集微域结合，并且这些多重相互作用是稳定整合素处于激活状态所必需的。►Talin FERM结构域具有新颖的开放构象►膜结合位点沿FERM结构域的一个表面分布►这些位点对于整合素激活和黏附聚集至关重要►线性Talin结构有利于整合素和膜的同时结合
FERM domains are found in a diverse superfamily of signaling and adaptor proteins at membrane interfaces. They typically consist of three separately folded domains (F1, F2, F3) in a compact cloverleaf structure. The crystal structure of the N-terminal head of the integrin-associated cytoskeletal protein talin reported here reveals a novel FERM domain with a linear domain arrangement, plus an additional domain F0 packed against F1. While F3 binds β-integrin tails, basic residues in F1 and F2 are required for membrane association and for integrin activation. We show that these same residues are also required for cell spreading and focal adhesion assembly in cells. We suggest that the extended conformation of the talin head allows simultaneous binding to integrins via F3 and to PtdIns(4,5)P2-enriched microdomains via basic residues distributed along one surface of the talin head, and that these multiple interactions are required to stabilize integrins in the activated state. ► Talin FERM domain has a novel open conformation ► Membrane association sites are distributed along one surface of the FERM domain ► These are critical for integrin activation and focal adhesion assembly ► Simultaneous integrin and membrane binding is favored by the linear talin structure
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
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影响因子：
64.8
作者：
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影响因子：
5.6
作者：
Goult BT;Bouaouina M;Harburger DS;Bate N;Patel B;Anthis NJ;Campbell ID;Calderwood DA;Barsukov IL;Roberts GC;Critchley DR
通讯作者：
Critchley DR
影响因子：
14.9
作者：
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通讯作者：
Richardson DC