1egx
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SOLUTION STRUCTURE OF THE ENA-VASP HOMOLOGY 1 (EVH1) DOMAIN OF HUMAN VASODILATOR-STIMULATED PHOSPHOPROTEIN (VASP)
OverviewOverview
The Ena-VASP family of proteins act as molecular adaptors linking the, cytoskeletal system to signal transduction pathways. Their N-terminal EVH1, domains use groups of exposed aromatic residues to specifically recognize, 'FPPPP' motifs found in the mammalian zyxin and vinculin proteins, and, ActA protein of the intracellular bacterium Listeria monocytogenes. Here, evidence is provided that the affinities of these EVH1-peptide, interactions are strongly dependent on the recognition of residues, flanking the core FPPPP motifs. Determination of the VASP EVH1 domain, solution structure, together with peptide library screening, measurement, of individual K(d)s by fluorescence titration, and NMR chemical shift, mapping, revealed a second affinity-determining epitope present in all, four ActA EVH1-binding motifs. The epitope was shown to interact with a, complementary hydrophobic site on the EVH1 surface and to increase, strongly the affinity of ActA for EVH1 domains. We propose that this, epitope, which is absent in the sequences of the native EVH1-interaction, partners zyxin and vinculin, may provide the pathogen with an advantage, when competing for the recruitment of the host VASP and Mena proteins in, the infected cell.
About this StructureAbout this Structure
1EGX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity., Ball LJ, Kuhne R, Hoffmann B, Hafner A, Schmieder P, Volkmer-Engert R, Hof M, Wahl M, Schneider-Mergener J, Walter U, Oschkinat H, Jarchau T, EMBO J. 2000 Sep 15;19(18):4903-14. PMID:10990454
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