Department of Biochemistry and Biophysics, Stockholm University, Science for Life Laboratory, Box 1031, 17121 Solna, Sweden.
J Mol Biol. 2021 Aug 20;433(17):167128. doi: 10.1016/j.jmb.2021.167128. Epub 2021 Jul 3.
The superfamily of pentameric ligand-gated ion channels (pLGICs) comprises key players in electrochemical signal transduction across evolution, including historic model systems for receptor allostery and targets for drug development. Accordingly, structural studies of these channels have steadily increased, and now approach 250 depositions in the protein data bank. This review contextualizes currently available structures in the pLGIC family, focusing on morphology, ligand binding, and gating in three model subfamilies: the prokaryotic channel GLIC, the cation-selective nicotinic acetylcholine receptor, and the anion-selective glycine receptor. Common themes include the challenging process of capturing and annotating channels in distinct functional states; partially conserved gating mechanisms, including remodeling at the extracellular/transmembrane-domain interface; and diversity beyond the protein level, arising from posttranslational modifications, ligands, lipids, and signaling partners. Interpreting pLGIC structures can be compared to describing an elephant in the dark, relying on touch alone to comprehend the many parts of a monumental beast: each structure represents a snapshot in time under specific experimental conditions, which must be integrated with further structure, function, and simulations data to build a comprehensive model, and understand how one channel may fundamentally differ from another.
五聚体配体门控离子通道（pLGIC）超家族包括跨进化电化学信号转导的关键参与者，包括受体变构的历史模型系统和药物开发的靶点。因此，这些通道的结构研究稳步增加，目前在蛋白质数据库中接近 250 个结构的沉积。本综述将目前可获得的 pLGIC 家族结构置于上下文中，重点关注三个模型亚家族的形态、配体结合和门控：原核通道 GLIC、阳离子选择性烟碱型乙酰胆碱受体和阴离子选择性甘氨酸受体。共同的主题包括捕获和注释不同功能状态下的通道这一具有挑战性的过程；部分保守的门控机制，包括细胞外/跨膜域界面的重塑；以及超越蛋白质水平的多样性，源于翻译后修饰、配体、脂质和信号伙伴。解释 pLGIC 结构可以比作在黑暗中描述大象，仅依靠触摸来理解巨兽的许多部分：每个结构代表在特定实验条件下的时间快照，必须与进一步的结构、功能和模拟数据相结合，以构建一个全面的模型，并了解一个通道如何从根本上不同于另一个通道。
