PDZ7 of glutamate receptor interacting protein binds to its target via a novel hydrophobic surface area
PDZ7 of glutamate receptor interacting protein binds to its target via a novel hydrophobic surface area
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DOI：
10.1074/jbc.m207206200
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发表时间：
2002-10-25
影响因子：
4.8
通讯作者：
Zhang, M
中科院分区：
文献类型：
--
作者：
Feng, W;Fan, JS;Zhang, M
谷氨酸受体相互作用蛋白1（GRIP 1）是由7个PDZ（Postsynaptic synaptic density-95/Discs large Zona occludens-1）结构域组成的支架蛋白。该蛋白在α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的突触靶向中起重要作用。GRIP 1 PDZ 7和Ras鸟嘌呤核苷酸交换因子GRASP-1之间的相互作用调节AMPA受体的突触分布。在这里，我们描述的三维结构的GRIP 1 PDZ 7确定的NMR光谱。GRIP 1 PDZ 7含有一个封闭的羧基结合口袋和一个狭窄的α B/β B-沟，不太可能与经典的PDZ配体结合。出乎意料的是，GRIP 1 PDZ 7在不同于常规配体结合α B/β B-沟的位点处含有大的溶剂暴露的疏水表面。NMR滴定实验表明GRIP 1 PDZ 7通过该疏水表面与GRASP-1结合。我们的数据揭示了一种新的PDZ结构域介导的蛋白质相互作用模式，可能是负责其他PDZ结构域的支架蛋白的多聚化。
Glutamate receptor interacting protein 1 (GRIP1) is a scaffold protein composed of seven PDZ (Postsynaptic synaptic density-95/Discs large Zona occludens-1) domains. The protein plays important roles in the synaptic targeting of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. The interaction between GRIP1 PDZ7 and a Ras guanine nucleotide exchange factor, GRASP-1, regulates synaptic distribution of AMPA receptors. Here, we describe the three-dimensional structure of GRIP1 PDZ7 determined by NMR spectroscopy. GRIP1 PDZ7 contains a closed carboxyl group-binding pocket and a narrow alphaB/betaB-groove that is not likely to bind to classical PDZ ligands. Unexpectedly, GRIP1 PDZ7 contains a large solvent-exposed hydrophobic surface at a site distinct from the conventional ligand-binding alphaB/betaB-groove. NMR titration experiments show that GRIP1 PDZ7 binds to GRASP-1 via this hydrophobic surface. Our data uncover a novel PDZ domain-mediated protein interaction mode that may be responsible for multimerization of other PDZ domain-containing scaffold proteins.