Crystal structure of vinculin in complex with vinculin binding site 50 (VBS50), the integrin binding site 2 (IBS2) of talin
- Globel Phasing
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 {angstrom} 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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- DODNIHOTHER U.S. STATES
- OSTI ID:
- 1038598
- Journal Information:
- Protein Sci., Journal Name: Protein Sci. Journal Issue: (4) ; 04, 2012 Vol. 21; ISSN 0961-8368
- Country of Publication:
- United States
- Language:
- ENGLISH
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