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Talin自抑制复合物的构象状态及力介导的激活

, PP. 604-613

Keywords: 细胞黏附,整合素,单分子生物物理学,分子动力学模拟,构象变化

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Abstract:

Talin是一类位于黏着斑上连接整合素及微丝细胞骨架的蛋白,具有承载和传递细胞内外应力的作用.其蛋白内部2个结构域F3和RS相互作用可以形成分子内自抑制构象,从而抑制与整合素的结合.使用原子力显微镜测量talin自抑制复合物两结构域间的结合强度,发现2者键寿命随作用力呈现弱的逆锁键特性,即在小力区间不随力的增加而减少,只有当力超过一定数值(10pN)后,才迅速降低.另外,分子动力学模拟研究发现了另一种除该自抑制复合物晶体结构之外的稳定构象.进一步分析显示,外力可能会调节这2种构象状态间的平衡关系,从而导致了生存几率的多重指数减小趋势.本实验发现了一种talin激活的负调节机制,为更好理解talin在黏着斑中的作用提供了新思路.

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