从结构生物学角度看NMDA受体药理学与功能
A structural biology perspective on NMDA receptor pharmacology and function.
作者信息
Regan Michael C, Romero-Hernandez Annabel, Furukawa Hiro
机构信息
Cold Spring Harbor Laboratory, WM Keck Structural Biology Laboratory, United States.
Cold Spring Harbor Laboratory, WM Keck Structural Biology Laboratory, United States; Watson School of Biological Sciences, United States.
出版信息
Curr Opin Struct Biol. 2015 Aug;33:68-75. doi: 10.1016/j.sbi.2015.07.012. Epub 2015 Aug 15.
Abstract
N-methyld-aspartate receptors (NMDARs) belong to the large family of ionotropic glutamate receptors (iGluRs), which are critically involved in basic brain functions as well as multiple neurological diseases and disorders. The NMDARs are large heterotetrameric membrane protein complexes. The extensive extracellular domains recognize neurotransmitter ligands and allosteric compounds and translate the binding information to regulate activity of the transmembrane ion channel. Here, we review recent advances in the structural biology of NMDARs with a focus on pharmacology and function. Structural analysis of the isolated extracellular domains in combination with the intact heterotetrameric NMDAR structure provides important insights into how this sophisticated ligand-gated ion channel may function.
摘要
N-甲基-D-天冬氨酸受体（NMDARs）属于离子型谷氨酸受体（iGluRs）大家族，这些受体在大脑基本功能以及多种神经疾病和紊乱中起着关键作用。NMDARs是大型异源四聚体膜蛋白复合物。广泛的细胞外结构域识别神经递质配体和变构化合物，并将结合信息转化为调节跨膜离子通道的活性。在此，我们综述NMDARs结构生物学的最新进展，重点关注药理学和功能。对分离的细胞外结构域的结构分析与完整的异源四聚体NMDAR结构相结合，为这种复杂的配体门控离子通道的功能提供了重要见解。
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