Department of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Trends Pharmacol Sci. 2010 Apr;31(4):161-74. doi: 10.1016/j.tips.2009.12.005. Epub 2010 Jan 25.
It is over forty years since the major neurotransmitters and their protein receptors were identified, and over twenty years since determination of the first amino-acid sequences of the Cys-loop receptors that recognize acetylcholine, serotonin, GABA and glycine. The last decade has seen the first structures of these proteins (and related bacterial and molluscan homologues) determined to atomic resolution. Hopefully over the next decade, more detailed molecular structures of entire Cys-loop receptors in drug-bound and drug-free conformations will become available. These, together with functional studies, will provide a clear picture of how these receptors participate in neurotransmission and how structural variations between receptor subtypes impart their unique characteristics. This insight should facilitate the design of novel and improved therapeutics to treat neurological disorders. This review considers our current understanding about the processes of agonist binding, receptor activation and channel opening, as well as allosteric modulation of the Cys-loop receptor family.
自主要神经递质及其蛋白质受体被鉴定以来已经过去了四十多年，自确定识别乙酰胆碱、血清素、GABA 和甘氨酸的第一个 Cys 环受体的氨基酸序列以来也已经过去了二十多年。在过去的十年中，这些蛋白质（以及相关的细菌和软体动物同源物）的第一个结构已被确定达到原子分辨率。希望在未来十年中，将有更多关于药物结合和非药物结合构象下整个 Cys 环受体的更详细的分子结构可用。这些结构连同功能研究将清楚地说明这些受体如何参与神经传递，以及受体亚型之间的结构差异如何赋予它们独特的特征。这种洞察力应该有助于设计新型和改进的疗法来治疗神经紊乱。这篇综述考虑了我们目前对激动剂结合、受体激活和通道打开过程的理解，以及 Cys 环受体家族的变构调节。
