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

被引：150

作者：

Beneken, J

Tu, JC

Xiao, B

Nuriya, M

Yuan, JP

Worley, PF

Leahy, DJ ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

来源：

NEURON | 2000年 / 26卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S0896-6273(00)81145-9

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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.

引用

页码：143 / 154

页数：12

共 74 条

[1]

Mutations in Drosophila enabled and rescue by human vasodilator-stimulated phosphoprotein (VASP) indicate important functional roles for Ena/VASP homology domain 1 (EVH1) and EVH2 domains [J].