1rkc
From Proteopedia
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| , resolution 2.70Å | |||||||
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| Gene: | VCL (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human vinculin head (1-258) in complex with talin's vinculin binding site 3 (residues 1944-1969)
Contents |
Overview
Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses.
Disease
Known disease associated with this structure: Cardiomyopathy, dilated, 1W OMIM:[193065]
About this Structure
1RKC is a Protein complex structure of sequences from Gallus gallus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Vinculin activation by talin through helical bundle conversion., Izard T, Evans G, Borgon RA, Rush CL, Bricogne G, Bois PR, Nature. 2004 Jan 8;427(6970):171-5. Epub 2003 Dec 31. PMID:14702644
Page seeded by OCA on Thu Mar 20 13:52:47 2008
