IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59798-9.html
   My bibliography  Save this article

Structural dynamics and permeability of the TRPV3 pentamer

Author

Listed:
  • Shifra Lansky

    (Weill Cornell Medicine
    Weizmann Institute of Science)

  • Zhaokun Wang

    (Weill Cornell Medicine)

  • Oliver B. Clarke

    (Columbia University Irving Medical Center
    Columbia University)

  • Christophe Chipot

    (Université de Lorraine
    University of Illinois at Urbana-Champaign
    The University of Chicago)

  • Simon Scheuring

    (Weill Cornell Medicine
    Weill Cornell Medicine)

Abstract

TRPV3 belongs to the large superfamily of tetrameric transient receptor potential (TRP) ion channels. Recently, using high-speed atomic force microscopy (HS-AFM), we discovered a rare and transient pentameric state for TRPV3 that is in equilibrium with the tetrameric state, and, using cryo-EM, we solved a low-resolution structure of the TRPV3 pentamer, in which, however, many residues were unresolved. Here, we present a higher resolution and more complete structure of the pentamer, revealing a domain-swapped architecture, a collapsed vanilloid binding site, and a large pore. Molecular dynamics simulations and potential of mean force calculations of the pentamer establish high protein dynamics and permeability to large cations. Subunit interface analysis, together with thermal denaturation experiments, led us to propose a molecular mechanism of the tetramer-to-pentamer transition, backed experimentally by HS-AFM observations. Collectively, our data demonstrate that the TRPV3 pentamer is in a hyper-activated state with unique, highly permissive permeation properties.

Suggested Citation

  • Shifra Lansky & Zhaokun Wang & Oliver B. Clarke & Christophe Chipot & Simon Scheuring, 2025. "Structural dynamics and permeability of the TRPV3 pentamer," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59798-9
    DOI: 10.1038/s41467-025-59798-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59798-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59798-9?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. Michael J. Caterina & Mark A. Schumacher & Makoto Tominaga & Tobias A. Rosen & Jon D. Levine & David Julius, 1997. "The capsaicin receptor: a heat-activated ion channel in the pain pathway," Nature, Nature, vol. 389(6653), pages 816-824, October.
    2. Shifra Lansky & John Michael Betancourt & Jingying Zhang & Yining Jiang & Elizabeth D. Kim & Navid Paknejad & Crina M. Nimigean & Peng Yuan & Simon Scheuring, 2023. "A pentameric TRPV3 channel with a dilated pore," Nature, Nature, vol. 621(7977), pages 206-214, September.
    3. Lejla Zubcevic & Mark A. Herzik & Mengyu Wu & William F. Borschel & Marscha Hirschi & Albert S. Song & Gabriel C. Lander & Seok-Yong Lee, 2018. "Conformational ensemble of the human TRPV3 ion channel," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Navid Paknejad & Vinay Sapuru & Richard K. Hite, 2023. "Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    Full references (including those not matched with items on IDEAS)

    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. Yang Li & Xuteng Lu & Xufeng Cheng & Keyu Xia & Junyan Hu & Peiyu Wang & Peiyuan Pang & Bomin Gao & Demeng Sun & Zhuzhen Zhang & Dongdong Li & Zengqin Deng & Changlin Tian & Chang Xie & Jing Yao, 2025. "Plant essential oil targets TRPV3 for skin renewal and structural mechanism of action," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    2. Zakir, HM & Mostafeezur, RM & Suzuki, A & Hitomi, S & Maeda, T & Seo, K & Yamada, Y & Yamamura, K & Lev, S & Binshtok, AM & Iwata, K & Kitagawa, J, 2012. "Expression of TRPV1 channels after nerve injury provides an essential delivery tool for neuropathic pain attenuation," MPRA Paper 50539, University Library of Munich, Germany.
    3. Sheryl E Koch & Elyse Martin & Amitesh Verma & Stacey Adjei & Jack Rubinstein, 2023. "Tefillin use induces preconditioning associated changes in heart rate variability," PLOS ONE, Public Library of Science, vol. 18(1), pages 1-15, January.
    4. Heng Zhang & Jia-Jia Lin & Ya-Kai Xie & Xiu-Zu Song & Jia-Yi Sun & Bei-Lei Zhang & Yun-Kun Qi & Zhen-Zhong Xu & Fan Yang, 2023. "Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Ruth A. Pumroy & Anna D. Protopopova & Tabea C. Fricke & Iris U. Lange & Ferdinand M. Haug & Phuong T. Nguyen & Pamela N. Gallo & Bárbara B. Sousa & Gonçalo J. L. Bernardes & Vladimir Yarov-Yarovoy & , 2022. "Structural insights into TRPV2 activation by small molecules," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Barbara Storti & Carmine Di Rienzo & Francesco Cardarelli & Ranieri Bizzarri & Fabio Beltram, 2015. "Unveiling TRPV1 Spatio-Temporal Organization in Live Cell Membranes," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-17, March.
    7. Zhongjie Ye & Nicola Galvanetto & Leonardo Puppulin & Simone Pifferi & Holger Flechsig & Melanie Arndt & Cesar Adolfo Sánchez Triviño & Michael Palma & Shifeng Guo & Horst Vogel & Anna Menini & Clemen, 2024. "Structural heterogeneity of the ion and lipid channel TMEM16F," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Junping Fan & Han Ke & Jing Lei & Jin Wang & Makoto Tominaga & Xiaoguang Lei, 2024. "Structural basis of TRPV1 inhibition by SAF312 and cholesterol," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    9. Maxim V Nikolaev & Natalia A Dorofeeva & Margarita S Komarova & Yuliya V Korolkova & Yaroslav A Andreev & Irina V Mosharova & Eugene V Grishin & Denis B Tikhonov & Sergey A Kozlov, 2017. "TRPV1 activation power can switch an action mode for its polypeptide ligands," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-16, May.
    10. Yining Jiang & Zhaokun Wang & Simon Scheuring, 2025. "A structural biology compatible file format for atomic force microscopy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    11. 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.
    12. Hossain Md Zakir & Rahman Md Mostafeezur & Akiko Suzuki & Suzuro Hitomi & Ikuko Suzuki & Takeyasu Maeda & Kenji Seo & Yoshiaki Yamada & Kensuke Yamamura & Shaya Lev & Alexander M Binshtok & Koichi Iwa, 2012. "Expression of TRPV1 Channels after Nerve Injury Provides an Essential Delivery Tool for Neuropathic Pain Attenuation," PLOS ONE, Public Library of Science, vol. 7(9), pages 1-12, September.
    13. Petra I Baeumler & Johannes Fleckenstein & Shin Takayama & Michael Simang & Takashi Seki & Dominik Irnich, 2014. "Effects of Acupuncture on Sensory Perception: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-40, December.
    14. Franziska L. Sendker & Tabea Schlotthauer & Christopher-Nils Mais & Yat Kei Lo & Mathias Girbig & Stefan Bohn & Thomas Heimerl & Daniel Schindler & Arielle Weinstein & Brian P. H. Metzger & Joseph W. , 2024. "Frequent transitions in self-assembly across the evolution of a central metabolic enzyme," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    15. Filomena Perri & Adriana Coricello & James D. Adams, 2020. "Monoterpenoids: The Next Frontier in the Treatment of Chronic Pain?," J, MDPI, vol. 3(2), pages 1-20, May.
    16. Luciano Maria Catalfamo & Giulia Marrone & Michele Basilicata & Ilaria Vivarini & Vincenza Paolino & David Della-Morte & Francesco Saverio De Ponte & Francesca Di Daniele & Domenico Quattrone & Danilo, 2022. "The Utility of Capsicum annuum L. in Internal Medicine and In Dentistry: A Comprehensive Review," IJERPH, MDPI, vol. 19(18), pages 1-20, September.
    17. Navid Paknejad & Vinay Sapuru & Richard K. Hite, 2023. "Structural titration reveals Ca2+-dependent conformational landscape of the IP3 receptor," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    18. Jongdae Won & Jinsung Kim & Hyeongseop Jeong & Jinhyeong Kim & Shasha Feng & Byeongseok Jeong & Misun Kwak & Juyeon Ko & Wonpil Im & Insuk So & Hyung Ho Lee, 2023. "Molecular architecture of the Gαi-bound TRPC5 ion channel," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Xiaolong Gao & Philipp A. M. Schmidpeter & Vladimir Berka & Ryan J. Durham & Chen Fan & Vasanthi Jayaraman & Crina M. Nimigean, 2022. "Gating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    20. Arthur Neuberger & Mai Oda & Yury A. Nikolaev & Kirill D. Nadezhdin & Elena O. Gracheva & Sviatoslav N. Bagriantsev & Alexander I. Sobolevsky, 2023. "Human TRPV1 structure and inhibition by the analgesic SB-366791," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

    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:16:y:2025:i:1:d:10.1038_s41467-025-59798-9. 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.