Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit
Structure of the zinc-bound amino-terminal domain of the NMDA receptor NR2B subunit
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DOI：
10.1038/emboj.2009.338
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发表时间：
2009-12-16
期刊：
影响因子：
11.4
通讯作者：
Furukawa, Hiro
中科院分区：
文献类型：
--
作者：
Karakas, Erkan;Simorowski, Noriko;Furukawa, Hiro
n -甲基- d -天冬氨酸（NMDA）受体属于嗜离子性谷氨酸受体（iGluRs）家族，在哺乳动物大脑中介导大部分快速兴奋性突触传递。NMDA受体功能的标志之一是，它们的离子通道活性是通过调节化合物与细胞外氨基末端结构域（ATD）的结合而变构调节的，而ATD与l -谷氨酸结合结构域不同。由于完全缺乏关于NMDA受体ATDs的结构信息，atd介导的变构调节的分子基础一直是谜。在这里，我们报道了NR2B NMDA受体亚基在无锌和锌结合状态下的ATD晶体结构。这些结构揭示了与非nmda受体ATDs不同的整体蛤壳状结构，以及锌结合位点、离子结合位点和假定的苯乙醇胺结合位点的分子决定因素。EMBO杂志，2009,28,3910-3920。doi: 10.1038 / emboj.2009.338;2009年11月12日在线发布
N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors (iGluRs) that mediate the majority of fast excitatory synaptic transmission in the mammalian brain. One of the hallmarks for the function of NMDA receptors is that their ion channel activity is allosterically regulated by binding of modulator compounds to the extracellular amino-terminal domain (ATD) distinct from the L-glutamate-binding domain. The molecular basis for the ATD-mediated allosteric regulation has been enigmatic because of a complete lack of structural information on NMDA receptor ATDs. Here, we report the crystal structures of ATD from the NR2B NMDA receptor subunit in the zinc-free and zinc-bound states. The structures reveal the overall clamshell-like architecture distinct from the non-NMDA receptor ATDs and molecular determinants for the zinc-binding site, ion-binding sites, and the architecture of the putative phenylethanolamine-binding site. The EMBO Journal (2009) 28, 3910-3920. doi: 10.1038/emboj.2009.338; Published online 12 November 2009