Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

作者:Yao Mingxi; Goult Benjamin T; Chen Hu; Cong Peiwen; Sheetz Michael P*; Yan Jie
来源:Scientific Reports, 2014, 4(1): 4610.
DOI:10.1038/srep04610

摘要

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at similar to 5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression.