Crystal structure of vinculin in complex with vinculin binding site 50 (VBS50), the integrin binding site 2 (IBS2) of talin

Protein Sci. 2012 Apr;21(4):583-8. doi: 10.1002/pro.2041. Epub 2012 Feb 28.


The cytoskeletal protein talin activates integrin receptors by binding of its FERM domain to the cytoplasmic tail of β-integrin. Talin also couples integrins to the actin cytoskeleton, largely by binding to and activating the cytoskeletal protein vinculin, which binds to F-actin through the agency of its five-helix bundle tail (Vt) domain. Talin activates vinculin by means of buried amphipathic α-helices coined vinculin binding sites (VBSs) that reside within numerous four- and five-helix bundle domains that comprise the central talin rod, which are released from their buried locales by means of mechanical tension on the integrin:talin complex. In turn, these VBSs bind to the N-terminal seven-helix bundle (Vh1) domain of vinculin, creating an entirely new helix bundle that severs its head-tail interactions. Interestingly, talin harbors a second integrin binding site coined IBS2 that consists of two five-helix bundle domains that also contain a VBS (VBS50). Here we report the crystal structure of VBS50 in complex with vinculin at 2.3 Å resolution and show that intramolecular interactions of VBS50 within IBS2 are much more extensive versus its interactions with vinculin. Indeed, the IBS2-vinculin interaction only occurs at physiological temperature and the affinity of VBS50 for vinculin is about 30 times less than other VBSs. The data support a model where integrin binding destabilizes IBS2 to allow it to bind to vinculin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry*
  • Binding Sites
  • Calorimetry
  • Focal Adhesions / chemistry
  • Humans
  • Integrins / chemistry*
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Stability
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry
  • Talin / chemistry*
  • Vinculin / chemistry*
  • X-Ray Diffraction


  • Actins
  • Integrins
  • Multiprotein Complexes
  • Receptors, Cell Surface
  • Talin
  • VCL protein, human
  • Vinculin

Associated data

  • PDB/4DJ9