1EGX

SOLUTION STRUCTURE OF THE ENA-VASP HOMOLOGY 1 (EVH1) DOMAIN OF HUMAN VASODILATOR-STIMULATED PHOSPHOPROTEIN (VASP)

Summary for 1EGX

• Entry DOI: 10.2210/pdb1egx/pdb
• Related: 1evh 1qc6
• Descriptor: VASODILATOR-STIMULATED PHOSPHOPROTEIN (1 entity in total)
• Functional Keywords: evh1, vasp-ena, poly-proline-binding domain, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P50552
• Total number of polymer chains: 1
• Total formula weight: 12746.36

Authors

Ball, L.,Kuhne, R.,Hoffmann, B.,Hafner, A.,Schmieder, P.,Volkmer-Engert, R.,Hof, M.,Wahl, M.,Schneider-Mergener, J.,Walter, U.,Oschkinat, H.,Jarchau, T. (deposition date: 2000-02-17, release date: 2000-09-20, Last modification date: 2024-05-01)

Primary citation

Ball, L.J.,Kuhne, R.,Hoffmann, B.,Hafner, A.,Schmieder, P.,Volkmer-Engert, R.,Hof, M.,Wahl, M.,Schneider-Mergener, J.,Walter, U.,Oschkinat, H.,Jarchau, T.
Dual epitope recognition by the VASP EVH1 domain modulates polyproline ligand specificity and binding affinity.
EMBO J., 19:4903-4914, 2000

PubMed Abstract: 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.

PubMed: 10990454
DOI: 10.1093/emboj/19.18.4903

Experimental method

SOLUTION NMR