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Structure of the voltage-gated calcium channel Cav1.1 at 3.6 Å resolution

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  • Jianping Wu

    (State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Zhen Yan

    (State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University)

  • Zhangqiang Li

    (State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Xingyang Qian

    (Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

  • Shan Lu

    (National Institute of Biological Sciences)

  • Mengqiu Dong

    (National Institute of Biological Sciences)

  • Qiang Zhou

    (State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University)

  • Nieng Yan

    (State Key Laboratory of Membrane Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University)

Abstract

The voltage-gated calcium (Cav) channels convert membrane electrical signals to intracellular Ca2+-mediated events. Among the ten subtypes of Cav channel in mammals, Cav1.1 is specified for the excitation–contraction coupling of skeletal muscles. Here we present the cryo-electron microscopy structure of the rabbit Cav1.1 complex at a nominal resolution of 3.6 Å. The inner gate of the ion-conducting α1-subunit is closed and all four voltage-sensing domains adopt an ‘up’ conformation, suggesting a potentially inactivated state. The extended extracellular loops of the pore domain, which are stabilized by multiple disulfide bonds, form a windowed dome above the selectivity filter. One side of the dome provides the docking site for the α2δ-1-subunit, while the other side may attract cations through its negative surface potential. The intracellular I–II and III–IV linker helices interact with the β1a-subunit and the carboxy-terminal domain of α1, respectively. Classification of the particles yielded two additional reconstructions that reveal pronounced displacement of β1a and adjacent elements in α1. The atomic model of the Cav1.1 complex establishes a foundation for mechanistic understanding of excitation–contraction coupling and provides a three-dimensional template for molecular interpretations of the functions and disease mechanisms of Cav and Nav channels.

Suggested Citation

  • Jianping Wu & Zhen Yan & Zhangqiang Li & Xingyang Qian & Shan Lu & Mengqiu Dong & Qiang Zhou & Nieng Yan, 2016. "Structure of the voltage-gated calcium channel Cav1.1 at 3.6 Å resolution," Nature, Nature, vol. 537(7619), pages 191-196, September.
  • Handle: RePEc:nat:nature:v:537:y:2016:i:7619:d:10.1038_nature19321
    DOI: 10.1038/nature19321
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    Cited by:

    1. Yiwei Gao & Shuai Xu & Xiaoli Cui & Hao Xu & Yunlong Qiu & Yiqing Wei & Yanli Dong & Boling Zhu & Chao Peng & Shiqi Liu & Xuejun Cai Zhang & Jianyuan Sun & Zhuo Huang & Yan Zhao, 2023. "Molecular insights into the gating mechanisms of voltage-gated calcium channel CaV2.3," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Ren, Xiufang & Lu, Yao & Luo, Jie & Zeng, Xudong, 2024. "Response solutions for a kind of quasi-periodic forced neuron system," Chaos, Solitons & Fractals, Elsevier, vol. 179(C).
    3. Cheng Zhao & Yuan Xie & Lizhen Xu & Fan Ye & Ximing Xu & Wei Yang & Fan Yang & Jiangtao Guo, 2022. "Structures of a mammalian TRPM8 in closed state," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Yiqing Wei & Zhuoya Yu & Lili Wang & Xiaojing Li & Na Li & Qinru Bai & Yuhang Wang & Renjie Li & Yufei Meng & Hao Xu & Xianping Wang & Yanli Dong & Zhuo Huang & Xuejun Cai Zhang & Yan Zhao, 2024. "Structural bases of inhibitory mechanism of CaV1.2 channel inhibitors," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Simone Pelizzari & Martin C. Heiss & Monica L. Fernández-Quintero & Yousra El Ghaleb & Klaus R. Liedl & Petronel Tuluc & Marta Campiglio & Bernhard E. Flucher, 2024. "CaV1.1 voltage-sensing domain III exclusively controls skeletal muscle excitation-contraction coupling," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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