The conformational states of talin autoinhibition complex and its activation under forces

Subjects: Biology >> Biophysics >> Biology submitted time 2016-05-12

Zeng Yan Zhang Yong Ji QingHua Lou JiZhong Song XianQiang Ye Sheng Zhang RongGuang Zeng Yan Song XianQiang Ji QingHua

Abstract： Talin is an integrin-binding protein located at focal adhesion site and serves as both an adapter and a force transmitter. Its integrin binding activity is regulated by the intramolecular autoinhibition interaction between its F3 and RS domains. Here, we used atomic force microscopy to measure the strength of talin autoinhibition complex. Our results suggest that the lifetime of talin autoinhibition complex shows weak catch bond behavior and does not change significantly at smaller forces, while it drops rapidly at larger forces (>10 pN). Moreover, besides the complex conformation revealed by crystal structure, our molecular dynamics (MD) simulations indicate the possible existence of another stable conformation. Further analysis indicates that forces may regulate the equilibrium of the two stable binding states and result in the non-exponential force dependence of the binding lifetime. Our findings reveal a negative regulation mechanism on talin activation and provide a new point of view on the function of talin in focal adhesion.

Peer Review Status:Awaiting Review

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