1xwj
From Proteopedia
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Vinculin head (1-258) in complex with the talin vinculin binding site 3 (1945-1969)
Overview
Talin is a key protein involved in linking integrins to the actin, cytoskeleton. The long flexible talin rod domain contains a number of, binding sites for vinculin, a cytoskeletal protein important in, stabilizing integrin-mediated cell-matrix junctions. Here we report the, solution structure of a talin rod polypeptide (residues 1843-1973) which, contains a single vinculin binding site (VBS; residues 1944-1969). Like, other talin rod polypeptides, it consists of a helical bundle, in this, case a four-helix bundle with a right-handed topology. The residues in the, VBS important for vinculin binding were identified by studying the binding, of a series of VBS-related peptides to the vinculin Vd1 domain. The key, binding determinants are buried in the interior of the helical bundle, suggesting that a substantial structural change in the talin polypeptide, is required for vinculin binding. Direct evidence for this was obtained by, NMR and EPR spectroscopy. [1H,15N]-HSQC spectra of the talin fragment, indicate that vinculin binding caused approximately two-thirds of the, protein to adopt a flexible random coil. For EPR spectroscopy, nitroxide, spin labels were attached to the talin polypeptide via appropriately, located cysteine residues. Measurements of inter-nitroxide distances in, doubly spin-labeled protein showed clearly that the helical bundle is, disrupted and the mobility of the helices, except for the VBS helix, is, markedly increased. Binding of vinculin to talin is thus a clear example, of the unusual phenomenon of protein unfolding being required for, protein/protein interaction.
About this Structure
1XWJ is a Protein complex structure of sequences from Gallus gallus. Full crystallographic information is available from OCA.
Reference
Structural and dynamic characterization of a vinculin binding site in the talin rod., Gingras AR, Vogel KP, Steinhoff HJ, Ziegler WH, Patel B, Emsley J, Critchley DR, Roberts GC, Barsukov IL, Biochemistry. 2006 Feb 14;45(6):1805-17. PMID:16460027
Page seeded by OCA on Wed Nov 21 06:23:33 2007
