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Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP

Author

Listed:
  • Risheng Wei

    (Peking University)

  • Qiang Chen

    (Shenzhen; Shenzhen)

  • Lei Zhang

    (Peking University)

  • Congcong Liu

    (Shenzhen Third People’s Hospital; Shenzhen)

  • Chuang Liu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Chang-Cheng Yin

    (Peking University)

  • Hongli Hu

    (Shenzhen; Shenzhen)

Abstract

The type-1 ryanodine receptor (RyR1) is an intracellular calcium release channel for skeletal muscle excitation-contraction coupling. Previous structural studies showed that the RyR1 activity is modulated by the exogenous regulators including caffeine, ryanodine, PCB-95 and diamide. An additional transmembrane helix, located adjacent to S1 and S4, has been observed in some structures, although its function remains unclear. Here, we report that using a mild purification procedure, this helix is co-purified with RyR1 and is designated as S0. When RyR1 is coupled with S0, it can be activated by Ca2+ to an open state; however when decoupled from S0, it remains in primed state. S0 regulates the channel conformation by directly affecting the TM domain via the pVSD-S0-S4/S5 linker coupling, which facilitates the dilation of S6. Our results demonstrate that S0 is an essential component of RyR1 and plays a key role in the physiological regulation of RyR1 channel gating.

Suggested Citation

  • Risheng Wei & Qiang Chen & Lei Zhang & Congcong Liu & Chuang Liu & Chang-Cheng Yin & Hongli Hu, 2025. "Structural insights into transmembrane helix S0 facilitated RyR1 channel gating by Ca2+/ATP," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57074-4
    DOI: 10.1038/s41467-025-57074-4
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    References listed on IDEAS

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    1. Kiarash Jamali & Lukas Käll & Rui Zhang & Alan Brown & Dari Kimanius & Sjors H. W. Scheres, 2024. "Automated model building and protein identification in cryo-EM maps," Nature, Nature, vol. 628(8007), pages 450-457, April.
    2. Kellie A. Woll & Omid Haji-Ghassemi & Filip Van Petegem, 2021. "Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Zhen Yan & Xiao-chen Bai & Chuangye Yan & Jianping Wu & Zhangqiang Li & Tian Xie & Wei Peng & Chang-cheng Yin & Xueming Li & Sjors H. W. Scheres & Yigong Shi & Nieng Yan, 2015. "Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution," Nature, Nature, vol. 517(7532), pages 50-55, January.
    4. Takuya Kobayashi & Akihisa Tsutsumi & Nagomi Kurebayashi & Kei Saito & Masami Kodama & Takashi Sakurai & Masahide Kikkawa & Takashi Murayama & Haruo Ogawa, 2022. "Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Ran Zalk & Oliver B. Clarke & Amédée des Georges & Robert A. Grassucci & Steven Reiken & Filippo Mancia & Wayne A. Hendrickson & Joachim Frank & Andrew R. Marks, 2015. "Structure of a mammalian ryanodine receptor," Nature, Nature, vol. 517(7532), pages 44-49, January.
    6. Deshun Gong & Ximin Chi & Jinhong Wei & Gewei Zhou & Gaoxingyu Huang & Lin Zhang & Ruiwu Wang & Jianlin Lei & S. R. Wayne Chen & Nieng Yan, 2019. "Modulation of cardiac ryanodine receptor 2 by calmodulin," Nature, Nature, vol. 572(7769), pages 347-351, August.
    7. Rouslan G. Efremov & Alexander Leitner & Ruedi Aebersold & Stefan Raunser, 2015. "Architecture and conformational switch mechanism of the ryanodine receptor," Nature, Nature, vol. 517(7532), pages 39-43, January.
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