4DJ9: Human Vinculin Head Domain Vh1 (Residues 1-258) In Complex With The Talin Vinculin Binding Site 50 (Vbs50, Residues 2078-2099)

The cytoskeletal protein talin activates integrin receptors by binding of its FERM domain to the cytoplasmic tail of beta-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 alpha-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 A 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.
PDB ID: 4DJ9Download
MMDB ID: 97695
PDB Deposition Date: 2012/2/1
Updated in MMDB: 2012/05
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 4DJ9: dimeric; determined by author and by software (PISA)
Molecular Components in 4DJ9
Label Count Molecule
Proteins (2 molecules)
Vinculin(Gene symbol: VCL)
Molecule annotation
Talin-1(Gene symbol: TLN1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB