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Cryo-EM structures of apo and antagonist-bound human Cav3.1

Author

Listed:
  • Yanyu Zhao

    (Westlake University
    Westlake Institute for Advanced Study
    Tsinghua University)

  • Gaoxingyu Huang

    (Tsinghua University)

  • Qiurong Wu

    (Tsinghua University)

  • Kun Wu

    (Capital Medical University)

  • Ruiqi Li

    (Capital Medical University)

  • Jianlin Lei

    (Tsinghua University)

  • Xiaojing Pan

    (Tsinghua University)

  • Nieng Yan

    (Tsinghua University
    Princeton University)

Abstract

Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1–Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain1–5. Here we report the cryo-electron microscopy structures of human Cav3.1 alone and in complex with a highly Cav3-selective blocker, Z9446,7, at resolutions of 3.3 Å and 3.1 Å, respectively. The arch-shaped Z944 molecule reclines in the central cavity of the pore domain, with the wide end inserting into the fenestration on the interface between repeats II and III, and the narrow end hanging above the intracellular gate like a plug. The structures provide the framework for comparative investigation of the distinct channel properties of different Cav subfamilies.

Suggested Citation

  • Yanyu Zhao & Gaoxingyu Huang & Qiurong Wu & Kun Wu & Ruiqi Li & Jianlin Lei & Xiaojing Pan & Nieng Yan, 2019. "Cryo-EM structures of apo and antagonist-bound human Cav3.1," Nature, Nature, vol. 576(7787), pages 492-497, December.
    • Handle: RePEc:nat:nature:v:576:y:2019:i:7787:d:10.1038_s41586-019-1801-3
    DOI: 10.1038/s41586-019-1801-3
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    Cited by:

    1. Xia Yao & Yan Wang & Zhifei Wang & Xiao Fan & Di Wu & Jian Huang & Alexander Mueller & Sarah Gao & Miaohui Hu & Carol V. Robinson & Yong Yu & Shuai Gao & Nieng Yan, 2022. "Structures of the R-type human Cav2.3 channel reveal conformational crosstalk of the intracellular segments," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. 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.

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