AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition
AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition
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DOI：
10.1093/emboj/17.16.4704
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发表时间：
1998-08-17
期刊：
影响因子：
11.4
通讯作者：
Keinänen, K
中科院分区：
文献类型：
--
作者：
Lampinen, M;Pentikäinen, O;Keinänen, K
为了确定配体识别的关键结构决定因素，我们对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）选择性谷氨酸受体GluR-D亚基的配体结合域进行定点诱变。基于对突变结合位点的[H-3]AMPA结合特性的分析，我们构建了一个修订的配体结合位点三维模型，该模型在许多方面与之前发布的模型不同。特别是，我们的结果表明残基Arg507和Glu727代表同源细菌赖氨酸/鸟氨酸/精氨酸结合蛋白和组氨酸结合蛋白中Arg77和Asp161的结构和功能相关性，并且分别直接与结合配体的α-羧基和α-氨基相互作用。相比之下，之前认为与激动剂的α-氨基发生离子相互作用的Glu424不太可能在配体结合中发挥这样的作用。我们的结果表明，谷氨酸受体与细菌极性氨基酸结合蛋白共享氨基酸识别的基本机制。
In order to identify key structural determinants for ligand recognition, we subjected the ligand-binding domain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor GluR-D subunit to site-directed mutagenesis. Based on the analysis of the [H-3]AMPA-binding properties of the mutated binding sites, we constructed a revised three-dimensional model of the ligand-binding site, different in many respects from previously published models. In particular, our results indicate that the residues Arg507 and Glu727 represent the structural and functional correlates of Arg77 and Asp161 in the homologous bacterial lysine/ornithine/arginine-binding protein and histidine-binding protein, and directly interact with the alpha-carboxyl and alpha-amino group of the bound ligand, respectively. In contrast, Glu424, implicated previously in ionic interactions with the a-amino group of the agonist, is unlikely to have such a role in ligand binding. Our results indicate that glutamate receptors share with the bacterial polar amino acid-binding proteins the fundamental mechanism of amino acid recognition.