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The conformational states of talin autoinhibition complex and its activation under forces
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  • 作者:Yan Zeng ; Yong Zhang ; XianQiang Song ; QingHua Ji ; Sheng Ye&#8230
  • 关键词:cell adhesion ; integrin signaling ; single molecule biophysics ; molecular dynamics simulations ; conformational changes
  • 刊名:Science China Life Sciences
  • 出版年:2015
  • 出版时间:July 2015
  • 年:2015
  • 卷:58
  • 期:7
  • 页码:694-703
  • 全文大小:1,118 KB
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  • 作者单位:Yan Zeng (1) (3)
    Yong Zhang (1)
    XianQiang Song (2) (3)
    QingHua Ji (1) (3)
    Sheng Ye (2)
    RongGuang Zhang (2)
    JiZhong Lou (1)

    1. Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
    3. University of Chinese Academy of Sciences, Beijing, 100049, China
    2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
  • 刊物主题:Life Sciences, general;
  • 出版者:Springer Berlin Heidelberg
  • ISSN:1869-1889
文摘
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.

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