IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30919-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30919-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30919-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    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. 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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Amy Clarke & Julia Skerjanz & Mathias A. F. Gsell & Patrick Wiedner & Hazel Erkan-Candag & Klaus Groschner & Thomas Stockner & Oleksandra Tiapko, 2024. "PIP2 modulates TRPC3 activity via TRP helix and S4-S5 linker," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Huiwen Chen & Zhanyi Xia & Jie Dong & Bo Huang & Jiangtao Zhang & Feng Zhou & Rui Yan & Yiqiang Shi & Jianke Gong & Juquan Jiang & Zhuo Huang & Daohua Jiang, 2024. "Structural mechanism of voltage-gated sodium channel slow inactivation," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Erick Olivares & Simón Salgado & Jean Paul Maidana & Gaspar Herrera & Matías Campos & Rodolfo Madrid & Patricio Orio, 2015. "TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-17, October.
    3. Jian Huang & Xiao Fan & Xueqin Jin & Sooyeon Jo & Hanxiong Bear Zhang & Akie Fujita & Bruce P. Bean & Nieng Yan, 2023. "Cannabidiol inhibits Nav channels through two distinct binding sites," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Lige Tonggu & Goragot Wisedchaisri & Tamer M. Gamal El-Din & Michael J. Lenaeus & Matthew M. Logan & Tatsuya Toma & Justin Bois & Ning Zheng & William A. Catterall, 2024. "Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Xingya Li & Gengping Jiang & Meipeng Jian & Chen Zhao & Jue Hou & Aaron W. Thornton & Xinyi Zhang & Jefferson Zhe Liu & Benny D. Freeman & Huanting Wang & Lei Jiang & Huacheng Zhang, 2023. "Construction of angstrom-scale ion channels with versatile pore configurations and sizes by metal-organic frameworks," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Purushotham Selvakumar & Ana I. Fernández-Mariño & Nandish Khanra & Changhao He & Alice J. Paquette & Bing Wang & Ruiqi Huang & Vaughn V. Smider & William J. Rice & Kenton J. Swartz & Joel R. Meyerson, 2022. "Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Hiroki Ota & Kimiaki Katanosaka & Shiori Murase & Makiko Kashio & Makoto Tominaga & Kazue Mizumura, 2013. "TRPV1 and TRPV4 Play Pivotal Roles in Delayed Onset Muscle Soreness," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-10, June.
    8. Ivo B. Regli & Giacomo Strapazzon & Marika Falla & Rosmarie Oberhammer & Hermann Brugger, 2021. "Long-Term Sequelae of Frostbite—A Scoping Review," IJERPH, MDPI, vol. 18(18), pages 1-16, September.
    9. Chenxi Lin & Yuxin Shan & Zhongyi Wang & Hui Peng & Rong Li & Pingzhou Wang & Junyan He & Weiwei Shen & Zhengxing Wu & Min Guo, 2024. "Molecular and circuit mechanisms underlying avoidance of rapid cooling stimuli in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Katsumasa Irie & Yoshinori Oda & Takashi Sumikama & Atsunori Oshima & Yoshinori Fujiyoshi, 2023. "The structural basis of divalent cation block in a tetrameric prokaryotic sodium channel," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    11. Carus H. Y. Lau & Emelie Flood & Mark J. Hunter & Billy J. Williams-Noonan & Karen M. Corbett & Chai-Ann Ng & James C. Bouwer & Alastair G. Stewart & Eduardo Perozo & Toby W. Allen & Jamie I. Vandenbe, 2024. "Potassium dependent structural changes in the selectivity filter of HERG potassium channels," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Ahmed Rohaim & Bram J. A. Vermeulen & Jing Li & Felix Kümmerer & Federico Napoli & Lydia Blachowicz & João Medeiros-Silva & Benoît Roux & Markus Weingarth, 2022. "A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. 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.
    14. Michael A Ha & Gregory J Smith & Joseph A Cichocki & Lu Fan & Yi-Shiuan Liu & Ana I Caceres & Sven Eric Jordt & John B Morris, 2015. "Menthol Attenuates Respiratory Irritation and Elevates Blood Cotinine in Cigarette Smoke Exposed Mice," PLOS ONE, Public Library of Science, vol. 10(2), pages 1-16, February.
    15. Jiangtao Zhang & Yiqiang Shi & Junping Fan & Huiwen Chen & Zhanyi Xia & Bo Huang & Juquan Jiang & Jianke Gong & Zhuo Huang & Daohua Jiang, 2022. "N-type fast inactivation of a eukaryotic voltage-gated sodium channel," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    16. Qiurong Wu & Jian Huang & Xiao Fan & Kan Wang & Xueqin Jin & Gaoxingyu Huang & Jiaao Li & Xiaojing Pan & Nieng Yan, 2023. "Structural mapping of Nav1.7 antagonists," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    17. Adam Lewis & Vilius Kurauskas & Marco Tonelli & Katherine Henzler-Wildman, 2021. "Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    18. Lilia Leisle & Kin Lam & Sepehr Dehghani-Ghahnaviyeh & Eva Fortea & Jason D. Galpin & Christopher A. Ahern & Emad Tajkhorshid & Alessio Accardi, 2022. "Backbone amides are determinants of Cl− selectivity in CLC ion channels," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Madeleine R. Wilcox & Aparna Nigam & Nathan G. Glasgow & Chamali Narangoda & Matthew B. Phillips & Dhilon S. Patel & Samaneh Mesbahi-Vasey & Andreea L. Turcu & Santiago Vázquez & Maria G. Kurnikova & , 2022. "Inhibition of NMDA receptors through a membrane-to-channel path," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Chiung-Wei Huang & Hsing-Jung Lai & Po-Yuan Huang & Ming-Jen Lee & Chung-Chin Kuo, 2016. "The Biophysical Basis Underlying Gating Changes in the p.V1316A Mutant Nav1.7 Channel and the Molecular Pathogenesis of Inherited Erythromelalgia," PLOS Biology, Public Library of Science, vol. 14(9), pages 1-31, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30919-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.