塔林1的架构揭示了自身抑制机制
Dirk Dedden1, Stephanie Schumacher1, Charlotte F Kelley1
1Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cell
|September 21, 2019
概括
塔林蛋白
科学领域:
- 细胞生物学
- 生物化学
- 结构生物学
背景情况:
- 焦点粘附 (FA) 对于细胞粘附,迁移和分化至关重要.
- 塔林是FA的关键组成部分,将整体与细胞骨连接起来.
- 了解塔林调节对于理解FA动态至关重要.
研究的目的:
- 阐明塔林功能的调节机制.
- 确定塔林自身抑制和激活的结构基础.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定全长塔林的结构.
- 生物化学测试以证明塔林的展开和形状变化.
主要成果:
- 一个冷EM结构揭示了talin1的双向自抑制机制.
- 作用素结合棒域形成一个紧的球状结构,由FERM头相互锁定.
- 特定的棒域 (R9和R12) 保护FERM域免受结合整体和PIP2的影响.
- 塔林1可逆地从紧展开到延伸的形状,暴露结合点.
结论:
- 塔林的自身抑制确保了整合蛋白,膜和细胞骨相互作用的协调调节.
- 塔林的合规切换对于调节FA循环和细胞信号是至关重要的.
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