title: Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition.
abstract: Homer EVH1 (Ena/VASP Homology 1) domains interact with proline-rich motifs in the cytoplasmic regions of group 1 metabotropic glutamate receptors (mGluRs), inositol-1,4,5-trisphosphate receptors (IP3Rs), and Shank proteins. We have determined the crystal structure of the Homer EVH1 domain complexed with a peptide from mGluR (TPPSPF). In contrast to other EVH1 domains, the bound mGluR ligand assumes an unusual conformation in which the side chains of the Ser-Pro tandem are oriented away from the Homer surface, and the Phe forms a unique contact. This unusual binding mode rationalizes conserved features of both Homer and Homer ligands that are not shared by other EVH1 domains. Site-directed mutagenesis confirms the importance of specific Homer residues for ligand binding. These results establish a molecular basis for understanding the biological properties of Homer-ligand complexes.
authors.affiliation: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J
authors.initials: J
authors.lastname: Beneken
authors.forename: J C
authors.initials: JC
authors.lastname: Tu
authors.forename: B
authors.initials: B
authors.lastname: Xiao
authors.forename: M
authors.initials: M
authors.lastname: Nuriya
authors.forename: J P
authors.initials: JP
authors.lastname: Yuan
authors.forename: P F
authors.initials: PF
authors.lastname: Worley
authors.forename: D J
authors.initials: DJ
authors.lastname: Leahy
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004926:Escherichia coli; D000072233:Homer Scaffolding Proteins; D008024:Ligands; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D009479:Neuropeptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D000072233:Homer Scaffolding Proteins; D008024:Ligands; D008840:Microfilament Proteins; D009479:Neuropeptides; D010455:Peptides; D018094:Receptors, Metabotropic Glutamate