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

Sci Rep. 2014 Apr 9;4:4610. doi: 10.1038/srep04610.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Focal Adhesions / metabolism
  • Magnetics
  • Mechanical Phenomena*
  • Molecular Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Folding*
  • Protein Structure, Tertiary
  • Stress, Mechanical
  • Surface Plasmon Resonance
  • Talin / metabolism*
  • Vinculin / metabolism*

Substances

  • Talin
  • Vinculin