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Structures of a mammalian TRPM8 in closed state

Author

Listed:
  • Cheng Zhao

    (Zhejiang University School of Medicine)

  • Yuan Xie

    (Fourth Military Medical University)

  • Lizhen Xu

    (Zhejiang University School of Medicine)

  • Fan Ye

    (Zhejiang University School of Medicine)

  • Ximing Xu

    (Ocean University of China)

  • Wei Yang

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Fan Yang

    (Zhejiang University School of Medicine
    Zhejiang University
    Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare
    Zhejiang University Medical Center)

  • Jiangtao Guo

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University Medical Center
    Zhejiang University)

Abstract

Transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable non-selective cation channel that acts as the primary cold sensor in humans. TRPM8 is also activated by ligands such as menthol, icilin, and phosphatidylinositol 4,5-bisphosphate (PIP2), and desensitized by Ca2+. Here we have determined electron cryo-microscopy structures of mouse TRPM8 in the absence of ligand, and in the presence of Ca2+ and icilin at 2.5–3.2 Å resolution. The ligand-free state TRPM8 structure represents the full-length structure of mammalian TRPM8 channels with a canonical S4-S5 linker and the clearly resolved selectivity filter and outer pore loop. TRPM8 has a short but wide selectivity filter which may account for its permeability to hydrated Ca2+. Ca2+ and icilin bind in the cytosolic-facing cavity of the voltage-sensing-like domain of TRPM8 but induce little conformational change. All the ligand-bound TRPM8 structures adopt the same closed conformation as the ligand-free structure. This study reveals the overall architecture of mouse TRPM8 and the structural basis for its ligand recognition.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30919-y
    DOI: 10.1038/s41467-022-30919-y
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    References listed on IDEAS

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    1. 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.
    2. Xu Zhang & Wenlin Ren & Paul DeCaen & Chuangye Yan & Xiao Tao & Lin Tang & Jingjing Wang & Kazuya Hasegawa & Takashi Kumasaka & Jianhua He & Jiawei Wang & David E. Clapham & Nieng Yan, 2012. "Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel," Nature, Nature, vol. 486(7401), pages 130-134, June.
    3. Thomas Voets & Guy Droogmans & Ulrich Wissenbach & Annelies Janssens & Veit Flockerzi & Bernd Nilius, 2004. "The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels," Nature, Nature, vol. 430(7001), pages 748-754, August.
    4. Luis G. Cuello & Vishwanath Jogini & D. Marien Cortes & Eduardo Perozo, 2010. "Structural mechanism of C-type inactivation in K+ channels," Nature, Nature, vol. 466(7303), pages 203-208, July.
    5. Jian Payandeh & Todd Scheuer & Ning Zheng & William A. Catterall, 2011. "The crystal structure of a voltage-gated sodium channel," Nature, Nature, vol. 475(7356), pages 353-358, July.
    6. David D. McKemy & Werner M. Neuhausser & David Julius, 2002. "Identification of a cold receptor reveals a general role for TRP channels in thermosensation," Nature, Nature, vol. 416(6876), pages 52-58, March.
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