Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.
Structure and gating mechanism of the α7 nicotinic acetylcholine receptor.
复制标题
α-7烟碱型乙酰胆碱受体的结构和门控机制。
DOI：
10.1016/j.cell.2021.02.049
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发表时间：
2021-04-15
期刊：
影响因子：
64.5
通讯作者：
Hibbs RE
中科院分区：
文献类型：
--
作者：
Noviello CM;Gharpure A;Mukhtasimova N;Cabuco R;Baxter L;Borek D;Sine SM;Hibbs RE
α7烟碱乙酰胆碱受体在中枢神经系统和胆碱能炎症通路中起关键作用。这种配体门控离子通道组装成同五聚体，对Ca 2+具有异常的渗透性，并且比任何其他Cys环受体更快地脱敏。α7受体是Cys环超家族的原型，但已被证明难以进行结构分析。我们目前的cryo-EM结构的人α7烟碱受体在休眠，激活和脱敏状态下，在门控周期的主要步骤照明的神经系统环境。这些结构还揭示了有助于其功能的元素，包括允许通道开放的C-末端闩锁，以及有助于其高电导和钙渗透性的细胞外前庭中的阴离子环。α7结构之间的比较为绘制门控周期提供了基础，并揭示了Cys环受体超家族中门控机制的分歧。门控周期三种主要构象状态（静息、活化和脱敏）下α7烟碱乙酰胆碱受体的冷冻-EM结构以及功能研究沿着揭示了钙传导和配体结合通道开放的变构偶联相关组分。
The α7 nicotinic acetylcholine receptor plays critical roles in the central nervous system and in the cholinergic inflammatory pathway. This ligand-gated ion channel assembles as a homopentamer, is exceptionally permeable to Ca2+, and desensitizes faster than any other Cys-loop receptor. The α7 receptor has served as a prototype for the Cys-loop superfamily yet has proven refractory to structural analysis. We present cryo-EM structures of the human α7 nicotinic receptor in a lipidic environment in resting, activated, and desensitized states, illuminating the principal steps in the gating cycle. The structures also reveal elements that contribute to its function, including a C-terminal latch that is permissive for channel opening, and an anionic ring in the extracellular vestibule that contributes to its high conductance and calcium permeability. Comparisons among the α7 structures provide a foundation for mapping the gating cycle and reveal divergence in gating mechanisms in the Cys-loop receptor superfamily. Cryo-EM structures of the α7 nicotinic acetylcholine receptor in three major conformational states of the gating cycle - resting, activated and desensitized - along with functional studies reveal components involved in calcium conductance and allosteric coupling of ligand binding to channel opening.
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DOI：
10.1085/jgp.100.3.373
发表时间：
1992-09
期刊：
The Journal of general physiology
影响因子：
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作者：
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