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本帖最后由 顾汉现 于 2021-11-29 17:38 编辑
Nature:天然甘氨酸受体的结构和组装机制
甘氨酸受体(GlyRs)形成氯渗透通道,在整个中枢神经系统中介导抑制信号的快速传导。甘氨酸和γ-氨基丁酸等为重要的中枢神经系统抑制性递质。本文为镇静催眠抗惊厥、降血压、改善脑机能、精神安定、促进睡眠等多种生理功能、神经精神科关联的基础科学研究论文。
(天然甘氨酸受体的结构和组装机制
甘氨酸受体(:GlyRS)是五聚体,“的Cys-环”受体,其形式氯化物可渗透通道并介导整个中枢神经系统中的快速抑制性信号1,2。在脊髓和脑干中,GlyRs 调节运动并在突变时引起运动障碍2 , 3。)
领研网
2021/11/28
论文
论文标题:Architecture and assembly mechanism of native glycine receptors
作者:Zhu, Hongtao, Gouaux, Eric
期刊:Nature
发表时间:2021/09/23
数字识别码:10.1038/s41586-021-04022-z
摘要:Glycine receptors (GlyRs) are pentameric, ‘Cys-loop’ receptors that form chloride-permeable channels and mediate fast inhibitory signalling throughout the central nervous system1,2. In the spinal cord and brainstem, GlyRs regulate locomotion and cause movement disorders when mutated2,3. However, the stoichiometry of native GlyRs and the mechanism by which they are assembled remain unclear, despite extensive investigation4,5,6,7,8. Here we report cryo-electron microscopy structures of native GlyRs from pig spinal cord and brainstem, revealing structural insights into heteromeric receptors and their predominant subunit stoichiometry of 4α:1β. Within the heteromeric pentamer, the β(+)–α(−) interface adopts a structure that is distinct from the α(+)–α(−) and α(+)–β(−) interfaces. Furthermore, the β-subunit contains a unique phenylalanine residue that resides within the pore and disrupts the canonical picrotoxin site. These results explain why inclusion of the β-subunit breaks receptor symmetry and alters ion channel pharmacology. We also find incomplete receptor complexes and, by elucidating their structures, reveal the architectures of partially assembled α-trimers and α-tetramers.
所属学科:
生物
神经科学
(导读 阿金)甘氨酸受体(GlyRs)形成氯渗透通道,在整个中枢神经系统中介导抑制信号的快速传导。本研究报告来自猪脊髓和脑干的天然GlyRs冷冻电镜结构,揭示了异构体受体及其4α:1β的亚基化学计量学结构。在异构五聚体中, β(+)–α(−) i界面结构不同于α(+)–α(−) 和α(+)–β(−)界面。而β-亚基包含苯丙氨酸残基。结构解析结果表明β-亚基打破受体对称性,改变离子通道的药理学机制。
文章标签
甘氨酸受体
离子通道
中枢神经系统
冷冻电镜结构
https://www.nature.com/articles/s41586-021-04022-z
https://www.linkresearcher.com/t ... d-afc1-d476e4af6fd2
甘氨酸受体
https://zh.wikipedia.org/wiki/%E ... 8%E5%8F%97%E4%BD%93
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