title: Diversity of polyproline recognition by EVH1 domains.
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.
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Francis C
authors.initials: FC
authors.lastname: Peterson
authors.forename: Brian F
authors.initials: BF
authors.lastname: Volkman
mesh_terms: D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010455:Peptides; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; C011083:polyproline