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The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel

Author

Listed:
  • Fan Yang

    (Zhejiang University School of Medicine
    University of California)

  • Xian Xiao

    (University of California
    Westlake University)

  • Bo Hyun Lee

    (University of California
    University of Washington, Department of Physiology and Biophysics)

  • Simon Vu

    (University of California)

  • Wei Yang

    (Zhejiang University School of Medicine)

  • Vladimir Yarov-Yarovoy

    (University of California)

  • Jie Zheng

    (University of California)

Abstract

The capsaicin receptor TRPV1 has been intensively studied by cryo-electron microscopy and functional tests. However, though the apo and capsaicin-bound structural models are available, the dynamic process of capsaicin activation remains intangible, largely due to the lack of a capsaicin-induced open structural model and the low occupancy of the transition states. Here we report that reducing temperature toward the freezing point substantially increased channel closure events even in the presence of saturating capsaicin. We further used a combination of fluorescent unnatural amino acid (fUAA) incorporation, computational modeling, and rate-equilibrium linear free-energy relationships analysis (Φ-analysis) to derive the fully open capsaicin-bound state model, and reveal how the channel transits from the apo to the open state. We observed that capsaicin initiates a conformational wave that propagates through the S4–S5 linker towards the S6 bundle and finally reaching the selectivity filter. Our study provides a temporal mechanism for capsaicin activation of TRPV1.

Suggested Citation

  • Fan Yang & Xian Xiao & Bo Hyun Lee & Simon Vu & Wei Yang & Vladimir Yarov-Yarovoy & Jie Zheng, 2018. "The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05339-6
    DOI: 10.1038/s41467-018-05339-6
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    Cited by:

    1. Chang-Run Guo & Zhong-Zhe Zhang & Xing Zhou & Meng-Yang Sun & Tian-Tian Li & Yun-Tao Lei & Yu-Hao Gao & Qing-Quan Li & Chen-Xi Yue & Yu Gao & Yi-Yu Lin & Cui-Yun Hao & Chang-Zhu Li & Peng Cao & Michae, 2023. "Chronic cough relief by allosteric modulation of P2X3 without taste disturbance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Do Hoon Kwon & Feng Zhang & Justin G. Fedor & Yang Suo & Seok-Yong Lee, 2022. "Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Marcos Matamoros & Xue Wen Ng & Joshua B. Brettmann & David W. Piston & Colin G. Nichols, 2023. "Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Yi-Yu Lin & Yan Lu & Chun-Yun Li & Xue-Fei Ma & Miao-Qing Shao & Yu-Hao Gao & Yu-Qing Zhang & Hai-Ning Jiang & Yan Liu & Yang Yang & Li-Dong Huang & Peng Cao & Heng-Shan Wang & Jin Wang & Ye Yu, 2024. "Finely ordered intracellular domain harbors an allosteric site to modulate physiopathological function of P2X3 receptors," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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