Structure of a eukaryotic cyclic-nucleotide-gated channel

Article

关键词: CRYSTAL-STRUCTURE;    C-LINKER;    FUNCTIONAL EXPRESSION;    LIGAND-BINDING;    ION PERMEATION;    CA2+ BLOCKAGE;    HCN CHANNELS;    K+ CHANNEL;    PORE;    SELECTIVITY;   

DOI  :  10.1038/nature20819

来源: SCIE

【 摘 要 】

Cyclic-nucleotide-gated channels are essential for vision and olfaction. They belong to the voltage-gated ion channel superfamily but their activities are controlled by intracellular cyclic nucleotides instead of transmembrane voltage. Here we report a 3.5-angstrom-resolution single-particle electron cryo-microscopy structure of a cyclic-nucleotide-gated channel from Caenorhabditis elegans in the cyclic guanosine monophosphate (cGMP)-bound open state. The channel has an unusual voltage-sensor-like domain, accounting for its deficient voltage dependence. A carboxy-terminal linker connecting S6 and the cyclic-nucleotide-binding domain interacts directly with both the voltage-sensor-like domain and the pore domain, forming a gating ring that couples conformational changes triggered by cyclic nucleotide binding to the gate. The selectivity filter is lined by the carboxylate side chains of a functionally important glutamate and three rings of backbone carbonyls. This structure provides a new framework for understanding mechanisms of ion permeation, gating and channelopathy of cyclic-nucleotide-gated channels and cyclic nucleotide modulation of related channels.

【 授权许可】

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