1ydi

From Proteopedia

Revision as of 18:12, 12 November 2007

Human Vinculin Head Domain (VH1, 1-258) in Complex with Human Alpha-Actinin's Vinculin-Binding Site (Residues 731-760)

Overview

Alpha-actinin and vinculin orchestrate reorganization of the actin, cytoskeleton following the formation of adhesion junctions. alpha-Actinin, interacts with vinculin through the binding of an alpha-helix (alphaVBS), present within the R4 spectrin repeat of its central rod domain to, vinculin's N-terminal seven-helical bundle domain (Vh1). The Vh1:alphaVBS, structure suggests that alphaVBS first unravels from its buried location, in the triple-helical R4 repeat to allow it to bind to vinculin. alphaVBS, binding then induces novel conformational changes in the N-terminal, helical bundle of Vh1, which disrupt its intramolecular association with, vinculin's tail domain and which differ from the alterations in Vh1, provoked by the binding of talin. Surprisingly, alphaVBS binds to Vh1 in, an inverted orientation compared to the binding of talin's VBSs to, vinculin. Importantly, the binding of alphaVBS and talin's VBSs to, vinculin's Vh1 domain appear to also trigger distinct conformational, changes in full-length vinculin, opening up distant regions that are, buried in the inactive molecule. The data suggest a model where vinculin's, Vh1 domain acts as a molecular switch that undergoes distinct structural, changes provoked by talin and alpha-actinin binding in focal adhesions, versus adherens junctions, respectively.

Disease

Known disease associated with this structure: Glomerulosclerosis, focal segmental, 1 OMIM:[604638]

About this Structure

1YDI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural dynamics of alpha-actinin-vinculin interactions., Bois PR, Borgon RA, Vonrhein C, Izard T, Mol Cell Biol. 2005 Jul;25(14):6112-22. PMID:15988023

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