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

ABSTRACT: 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 ?5?pN, suggesting that 5?pN is the force threshold for vinculin binding and adhesion progression.

SUBMITTER: Yao M 

PROVIDER: S-EPMC3980218 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature