Beneken J, Tu J C, Xiao B, Nuriya M, Yuan J P, Worley P F, Leahy D J
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 2000 Apr;26(1):143-54. doi: 10.1016/s0896-6273(00)81145-9.
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.
荷马EVH1（Ena/VASP同源结构域1）结构域与1型代谢型谷氨酸受体（mGluRs）、肌醇-1,4,5-三磷酸受体（IP3Rs）及Shank蛋白胞质区域富含脯氨酸的基序相互作用。我们已确定了与来自mGluR的肽（TPPSPF）复合的荷马EVH1结构域的晶体结构。与其他EVH1结构域不同，结合的mGluR配体呈现出一种不寻常的构象，其中Ser-Pro串联的侧链远离荷马表面，且苯丙氨酸形成独特的接触。这种不寻常的结合模式解释了荷马及其配体中不为其他EVH1结构域所共有的保守特征。定点诱变证实了特定荷马残基对配体结合的重要性。这些结果为理解荷马-配体复合物的生物学特性奠定了分子基础。
