4DJ9

Human vinculin head domain Vh1 (residues 1-258) in complex with the talin vinculin binding site 50 (VBS50, residues 2078-2099)

Summary for 4DJ9

• Entry DOI: 10.2210/pdb4dj9/pdb
• Related: 1rkc 1rke 1syq 3s90 3tj5 3tj6
• Descriptor: Vinculin, Talin-1 (3 entities in total)
• Functional Keywords: cytoskeleton, focal adhesion, protein-protein interaction, four-helix bundle, cell adhesion, f-actin, cytosol
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton: P18206; Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): Q9Y490
• Total number of polymer chains: 2
• Total formula weight: 31807.72

Authors

Yogesha, S.D.,Rangarajan, E.S.,Vonrhein, C.,Bricogne, G.,Izard, T. (deposition date: 2012-02-01, release date: 2012-02-29, Last modification date: 2024-02-28)

Primary citation

Yogesha, S.D.,Rangarajan, E.S.,Vonrhein, C.,Bricogne, G.,Izard, T.
Crystal structure of vinculin in complex with vinculin binding site 50 (VBS50), the integrin binding site 2 (IBS2) of talin.
Protein Sci., 21:583-588, 2012

PubMed Abstract: 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.

PubMed: 22334306
DOI: 10.1002/pro.2041

Experimental method

X-RAY DIFFRACTION (2.25 Å)