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

作　　者：ZENG Yan ZHANG Yong SONG XianQiang JI QingHua YE Sheng ZHANG RongGuang LOU JiZhong 

机构地区：[1]Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences [2]University of Chinese Academy of Sciences [3]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

出　　处：《Science China(Life Sciences)》2015年第7期694-703,共10页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China(2014CB910202);National Natural Science Foundation of China(11302240,31070827 and 31222022)

摘　　要：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 p N). 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.Talin is an integrin-binding protein located at focal adhesion site and serves as both an adapter and a force transmitter. Its in- tegrin 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.

关 键 词：cell adhesion integrin signaling single molecule biophysics molecular dynamics simulations conformational changes 

分 类 号：Q51[生物学—生物化学]