Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition

Jutta Beneken, Jian Cheng Tu, Bo Xiao, Mutsuo Nuriya, Joseph P. Yuan, Paul F. Worley, Daniel J. Leahy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)143-154
Number of pages12
JournalNeuron
Volume26
Issue number1
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Neuroscience(all)

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