title: The conformational states of talin autoinhibition complex and its activation under forces.
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.
authors.affiliation: Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: XianQiang
authors.initials: X
authors.lastname: Song
authors.forename: QingHua
authors.initials: Q
authors.lastname: Ji
authors.forename: Sheng
authors.initials: S
authors.lastname: Ye
authors.forename: RongGuang
authors.initials: R
authors.lastname: Zhang
authors.forename: JiZhong
authors.initials: J
authors.lastname: Lou
mesh_terms: D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D016608:Talin / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D016608:Talin