Burgos Carlos F, Yévenes Gonzalo E, Aguayo Luis G
Laboratory of Neurophysiology (C.F.B., L.G.A.), and Laboratory of Neuropharmacology (G.E.Y.), Department of Physiology, University of Concepción, Concepción, Chile.
Laboratory of Neurophysiology (C.F.B., L.G.A.), and Laboratory of Neuropharmacology (G.E.Y.), Department of Physiology, University of Concepción, Concepción, Chile
Mol Pharmacol. 2016 Sep;90(3):318-25. doi: 10.1124/mol.116.105726. Epub 2016 Jul 11.
Glycine receptors (GlyR) are inhibitory Cys-loop ion channels that contribute to the control of excitability along the central nervous system (CNS). GlyR are found in the spinal cord and brain stem, and more recently they were reported in higher regions of the CNS such as the hippocampus and nucleus accumbens. GlyR are involved in motor coordination, respiratory rhythms, pain transmission, and sensory processing, and they are targets for relevant physiologic and pharmacologic modulators. Several studies with protein crystallography and cryoelectron microscopy have shed light on the residues and mechanisms associated with the activation, blockade, and regulation of pentameric Cys-loop ion channels at the atomic level. Initial studies conducted on the extracellular domain of acetylcholine receptors, ion channels from prokaryote homologs-Erwinia chrysanthemi ligand-gated ion channel (ELIC), Gloeobacter violaceus ligand-gated ion channel (GLIC)-and crystallized eukaryotic receptors made it possible to define the overall structure and topology of the Cys-loop receptors. For example, the determination of pentameric GlyR structures bound to glycine and strychnine have contributed to visualizing the structural changes implicated in the transition between the open and closed states of the Cys-loop receptors. In this review, we summarize how the new information obtained in functional, mutagenesis, and structural studies have contributed to a better understanding of the function and regulation of GlyR.
甘氨酸受体（GlyR）是抑制性半胱氨酸环离子通道，有助于控制中枢神经系统（CNS）的兴奋性。GlyR存在于脊髓和脑干中，最近在中枢神经系统的更高区域如海马体和伏隔核中也有报道。GlyR参与运动协调、呼吸节律、疼痛传递和感觉处理，并且它们是相关生理和药理调节剂的作用靶点。几项利用蛋白质晶体学和冷冻电子显微镜进行的研究，在原子水平上揭示了与五聚体半胱氨酸环离子通道的激活、阻断和调节相关的残基和机制。最初对乙酰胆碱受体的细胞外结构域、原核生物同源物——菊欧文氏菌配体门控离子通道（ELIC）、紫球藻配体门控离子通道（GLIC）的离子通道以及结晶的真核受体进行的研究，使得确定半胱氨酸环受体的整体结构和拓扑结构成为可能。例如，与甘氨酸和士的宁结合的五聚体GlyR结构的确定，有助于直观呈现半胱氨酸环受体在开放和关闭状态转变过程中涉及的结构变化。在这篇综述中，我们总结了功能、诱变和结构研究中获得的新信息如何有助于更好地理解GlyR的功能和调节。
