The structural basis of integrin-linked kinase-PINCH interactions
The structural basis of integrin-linked kinase-PINCH interactions
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DOI：
10.1073/pnas.0811415106
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发表时间：
2008-12-30
影响因子：
11.1
通讯作者：
Calderwood, David A.
中科院分区：
文献类型：
--
作者：
Chiswell, Brian P.;Zhang, Rong;Calderwood, David A.
整合素连接激酶 (ILK)、PINCH 和 parvin 之间的异三聚体复合物是一个重要的信号传导平台，充当整合素和生长因子信号传导的汇聚点，并调节细胞粘附、扩散和迁移。我们报告了与 PINCH1 LIM1 结构域结合的 ILK 锚蛋白重复结构域的 1.6 埃晶体结构，揭示了 ILK-PINCH 相互作用的分子基础，并提供了 ILK 该区域的结构描述。该结构识别了 ILK 中的 5 个锚蛋白重复序列，解释了之前的缺失诱变数据，允许识别破坏相互作用的 ILK 和 PINCH1 点突变，显示了 PINCH1 LIM1 如何协调锌，并表明 LIM1 结构域内 2 个锌指之间的构象灵活性和扭曲可能对 ILK 结合很重要。这些数据提供了 ILK-PINCH-parvin 支架复合物中关键相互作用的原子分辨率描述。
The heterotrimeric complex between integrin-linked kinase ( ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. We report a 1.6-angstrom crystal structure of the ILK ankyrin repeat domain bound to the PINCH1 LIM1 domain, revealing the molecular basis of ILK-PINCH interactions and providing a structural description of this region of ILK. This structure identifies 5 ankyrin repeats in ILK, explains previous deletion mutagenesis data, permits identification of ILK and PINCH1 point mutations that disrupt the interaction, shows how zincs are coordinated by PINCH1 LIM1, and suggests that conformational flexibility and twisting between the 2 zinc fingers within the LIM1 domain may be important for ILK binding. These data provide an atomic-resolution description of a key interaction in the ILK-PINCH-parvin scaffolding complex.