Download MendeleyStructure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition.
Beneken, J., Tu, J.C., Xiao, B., Nuriya, M., Yuan, J.P., Worley, P.F., Leahy, D.J.(2000) Neuron 26: 143-154
- PubMed: 10798399
- DOI: https://doi.org/10.1016/s0896-6273(00)81145-9
- Primary Citation of Related Structures:
1DDV, 1DDW - PubMed 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.
Organizational Affiliation:
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
