@article{838108cd60a9440e959ebcedb4ccaa6c,
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.",
author = "Jutta Beneken and Tu, {Jian Cheng} and Bo Xiao and Mutsuo Nuriya and Yuan, {Joseph P.} and Worley, {Paul F.} and Leahy, {Daniel J.}",
note = "Funding Information: We thank C. Dann, K. Ramyar, C. Ogata, and the staff at beamline X4A for their assistance in data collection; the JHMI DNA/Protein/Peptide Facility for peptide synthesis and purification; S. Gabelli for her assistance with AMoRe; W. Lim for suggesting the use of minimal peptides for cocrystallization. This work was supported by grants to P. F. W. from the National Institute on Drug Abuse and the National Institute of Mental Health and to D. J. L. from the National Institutes of Health. D. J. L. is an assistant investigator of the Howard Hughes Medical Institute. We also wish to acknowledge a special debt to the late Daniel Nathans for inspiring and supporting early stages of this work; he is sorely missed.",
year = "2000",
doi = "10.1016/S0896-6273(00)81145-9",
language = "English",
volume = "26",
pages = "143--154",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",
}