Nature:谷氨酸受体通道开放至亚电导水平 兴奋性传递

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Nature:谷氨酸受体通道开放至亚电导水平  兴奋性神经传递

谷氨酸受体(iGluRs) 是四聚体离子通道，可介导中枢神经系统1中的大部分兴奋性神经传递。

领研网
·
2022/05/15

论文
论文标题：Opening of glutamate receptor channel to subconductance levels
作者：Maria V. Yelshanskaya, Dhilon S. Patel, Christopher M. Kottke, Maria G. Kurnikova & Alexander I. Sobolevsky
期刊：Nature
发表时间：2022/04/20
数字识别码：10.1038/s41586-022-04637-w
摘要：Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate1,2,3. An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1–O4)4,5,6. Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)6,7,8,9,10. Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit γ2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.

所属学科：
结构生物学
（导读 阿金）离子型谷氨酸受体（iGluRs）通道会打开孔核以响应激动剂谷氨酸的结合。本研究解析出AMPA亚型iGluR和辅助型亚基γ2突触复合物在非脱敏条件下的结构，发现谷氨酸只有在与至少相同数量属于亚基A和C的配体结合结构域（LBDs）结合后，才会结合亚基B和D的LBDs，而通道打开要求激动剂至少与两个LBDs结合。亚基独立性的缺乏、谷氨酸与通道打开的低效率偶联是突触复合物的门控，为上调突触活动提供可能。

文章标签
离子型谷氨酸受体
激动剂
非脱敏条件
谷氨酸
配体结合结构域

https://www.nature.com/articles/s41586-022-04637-w

https://www.linkresearcher.com/t ... 0-b543-6c466388cd7e



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