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Diversity of polyproline recognition by EVH1 domains. Front Biosci (Landmark Ed) 2009 Jan 01;14:833-46 PMID: 19273103 PMCID: PMC3882067

Abstract

Enabled/VASP Homology-1 (EVH1) domains function primarily as interaction modules that link signaling proteins by binding to proline-rich sequences. EVH1 domains are ~115 residues in length and adopt the pleckstrin homology (PH) fold. Four different protein families contain EVH1 domains: Ena/VASP, Homer, WASP and SPRED. Except for the SPRED domains, for which no binding partners are known, EVH1 domains use a conserved hydrophobic cleft to bind a four-residue motif containing 2-4 prolines. Conserved aromatic residues, including an invariant tryptophan, create a wedge-shaped groove on the EVH1 surface that matches the triangular profile of a polyproline type II helix. Hydrophobic residues adjacent to the polyproline motif dock into complementary sites on the EVH1 domain to enhance ligand binding specificity. Pseudosymmetry in the polyproline type II helix allows peptide ligands to bind in either of two N-to-C terminal orientations, depending on interactions between sequences flanking the prolines and the EVH1 domain. EVH1 domains also recognize non-proline motifs, as illustrated by the structure of an EVH1:LIM3 complex and the extended EVH1 ligands of the verprolin family.

Author List

Peterson FC, Volkman BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Adhesion Molecules
Microfilament Proteins
Peptides
Phosphoproteins
Substrate Specificity



View this publication's entry at the Pubmed website PMID: 19273103
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