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Structure of a eukaryotic cyclic-nucleotide-gated channel

Author

Listed:
  • Minghui Li

    (Columbia University)

  • Xiaoyuan Zhou

    (Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Shu Wang

    (Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences
    Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences
    Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming College of Life Science, University of Chinese Academy of Sciences)

  • Ioannis Michailidis

    (Columbia University)

  • Ye Gong

    (Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences
    Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences
    Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences)

  • Deyuan Su

    (Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences
    Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences
    Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming College of Life Science, University of Chinese Academy of Sciences)

  • Huan Li

    (Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences
    Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences
    Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences
    Kunming College of Life Science, University of Chinese Academy of Sciences)

  • Xueming Li

    (Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Jian Yang

    (Columbia University
    Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences
    Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences
    Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences)

Abstract

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-Å-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.

Suggested Citation

  • Minghui Li & Xiaoyuan Zhou & Shu Wang & Ioannis Michailidis & Ye Gong & Deyuan Su & Huan Li & Xueming Li & Jian Yang, 2017. "Structure of a eukaryotic cyclic-nucleotide-gated channel," Nature, Nature, vol. 542(7639), pages 60-65, February.
  • Handle: RePEc:nat:nature:v:542:y:2017:i:7639:d:10.1038_nature20819
    DOI: 10.1038/nature20819
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    Citations

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    Cited by:

    1. Zhengshan Hu & Xiangdong Zheng & Jian Yang, 2023. "Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Vishal R. Patel & Arturo M. Salinas & Darong Qi & Shipra Gupta & David J. Sidote & Marcel P. Goldschen-Ohm, 2021. "Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Adam Lewis & Vilius Kurauskas & Marco Tonelli & Katherine Henzler-Wildman, 2021. "Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    4. Xiaolong Gao & Philipp A. M. Schmidpeter & Vladimir Berka & Ryan J. Durham & Chen Fan & Vasanthi Jayaraman & Crina M. Nimigean, 2022. "Gating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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