IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30537-8.html
   My bibliography  Save this article

Structural mechanism of TRPV3 channel inhibition by the anesthetic dyclonine

Author

Listed:
  • Arthur Neuberger

    (Columbia University)

  • Kirill D. Nadezhdin

    (Columbia University)

  • Alexander I. Sobolevsky

    (Columbia University)

Abstract

Skin diseases are common human illnesses that occur in all cultures, at all ages, and affect between 30% and 70% of individuals globally. TRPV3 is a cation-permeable TRP channel predominantly expressed in skin keratinocytes, implicated in cutaneous sensation and associated with numerous skin diseases. TRPV3 is inhibited by the local anesthetic dyclonine, traditionally used for topical applications to relieve pain and itch. However, the structural basis of TRPV3 inhibition by dyclonine has remained elusive. Here we present a cryo-EM structure of a TRPV3-dyclonine complex that reveals binding of the inhibitor in the portals which connect the membrane environment surrounding the channel to the central cavity of the channel pore. We propose a mechanism of TRPV3 inhibition in which dyclonine molecules stick out into the channel pore, creating a barrier for ion conductance. The allosteric binding site of dyclonine can serve as a template for the design of new TRPV3-targeting drugs.

Suggested Citation

  • Arthur Neuberger & Kirill D. Nadezhdin & Alexander I. Sobolevsky, 2022. "Structural mechanism of TRPV3 channel inhibition by the anesthetic dyclonine," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30537-8
    DOI: 10.1038/s41467-022-30537-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30537-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30537-8?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. Takashi Miyamoto & Matt J. Petrus & Adrienne E. Dubin & Ardem Patapoutian, 2011. "TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin," Nature Communications, Nature, vol. 2(1), pages 1-12, September.
    2. G. D. Smith & M. J. Gunthorpe & R. E. Kelsell & P. D. Hayes & P. Reilly & P. Facer & J. E. Wright & J. C. Jerman & J.-P. Walhin & L. Ooi & J. Egerton & K. J. Charles & D. Smart & A. D. Randall & P. An, 2002. "TRPV3 is a temperature-sensitive vanilloid receptor-like protein," Nature, Nature, vol. 418(6894), pages 186-190, July.
    3. Haoxing Xu & I. Scott Ramsey & Suhas A. Kotecha & Magdalene M. Moran & Jayhong A. Chong & Deborah Lawson & Pei Ge & Jeremiah Lilly & Inmaculada Silos-Santiago & Yu Xie & Peter S. DiStefano & Rory Curt, 2002. "TRPV3 is a calcium-permeable temperature-sensitive cation channel," Nature, Nature, vol. 418(6894), pages 181-186, July.
    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. Arthur Neuberger & Yury A. Trofimov & Maria V. Yelshanskaya & Jeffrey Khau & Kirill D. Nadezhdin & Lena S. Khosrof & Nikolay A. Krylov & Roman G. Efremov & Alexander I. Sobolevsky, 2023. "Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Arthur Neuberger & Yury A. Trofimov & Maria V. Yelshanskaya & Kirill D. Nadezhdin & Nikolay A. Krylov & Roman G. Efremov & Alexander I. Sobolevsky, 2023. "Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Kirill D. Nadezhdin & Irina A. Talyzina & Aravind Parthasarathy & Arthur Neuberger & David X. Zhang & Alexander I. Sobolevsky, 2023. "Structure of human TRPV4 in complex with GTPase RhoA," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. 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.

    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. Jing Lei & Reiko U. Yoshimoto & Takeshi Matsui & Masayuki Amagai & Mizuho A. Kido & Makoto Tominaga, 2023. "Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:13:y:2022:i:1:d:10.1038_s41467-022-30537-8. 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.