Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition
Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition
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DOI：
10.1016/s0896-6273(00)81145-9
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发表时间：
2000-04-01
期刊：
影响因子：
16.2
通讯作者：
Leahy, DJ
中科院分区：
文献类型：
--
作者：
Beneken, J;Tu, JC;Leahy, DJ
Homer EVH 1（Ena/VASP同源1）结构域与第1组代谢型谷氨酸受体（mGluR）、肌醇-1，4，5-三磷酸受体（IP 3R）和Shank蛋白质的胞质区域中富含脯氨酸的基序相互作用。我们已经确定了与来自mGluR（TPPSPF）的肽复合的Homer EVH 1结构域的晶体结构。与其他EVH 1结构域相反，结合的mGluR配体呈现不寻常的构象，其中Ser-Pro串联体的侧链远离Homer表面取向，并且Phe形成独特的接触。这种不寻常的结合模式合理化的保守功能的荷马和荷马配体不共享的其他EVH 1域。定点诱变证实了特异性Homer残基对于配体结合的重要性。这些结果为理解Homer-配体复合物的生物学性质奠定了分子基础。
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.