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Abstract：
Mammalian cyclic nucleotide-gated (CNG) channels play an essential role in the signal transduction of the visual and olfactory sensory systems. Here we reveal the structural mechanism of ligand gating in human rod CNGA1 channel by determining its cryo-EM structures in both the apo closed and cGMP-bound open states. Distinct from most other members of voltage-gated tetrameric cation channels, CNGA1 forms a central channel gate in the middle of the membrane, occluding the central cavity. Structural analyses of ion binding profiles in the selectivity filters of the wild-type channel and the E365Q filter mutant allow us to unambiguously define the two Ca2+ binding sites inside the selectivity filter, providing structural insights into Ca2+ blockage and permeation in CNG channels. The structure of the E365Q mutant also reveals two alternative side-chain conformations at Q365, providing a plausible explanation for the voltage-dependent gating of CNG channel acquired upon E365 mutation.
摘要：
哺乳动物环核苷酸门控（CNG）通道在视觉和嗅觉感觉系统的信号转导中起着至关重要的作用。在这里，我们通过确定人棒CNGA1通道在apo封闭状态和cGMP结合开放状态下的cryo-EM结构，揭示了配体门控的结构机制。与电压门控四聚体阳离子通道的大多数其他成员不同，CNGA1在膜的中间形成一个中央通道门，封闭中央腔。野生型通道和E365Q过滤器突变体的选择性过滤器中离子结合谱的结构分析使我们能够明确定义选择性过滤器内的两个Ca2结合位点，提供对CNG通道中Ca2+堵塞和渗透的结构见解。E365Q突变体的结构还揭示了Q365处的两个替代侧链构象,为E365突变后获得的CNG通道的电压依赖性门控提供了合理的解释。
