IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36579-w.html
   My bibliography  Save this article

A bivalent remipede toxin promotes calcium release via ryanodine receptor activation

Author

Listed:
  • Michael J. Maxwell

    (The University of Queensland)

  • Chris Thekkedam

    (Australian National University
    Victor Chang Cardiac Research Institute)

  • Cedric Lamboley

    (The University of Queensland)

  • Yanni K.-Y. Chin

    (The University of Queensland)

  • Theo Crawford

    (The University of Queensland)

  • Jennifer J. Smith

    (The University of Queensland)

  • Junyu Liu

    (The University of Queensland)

  • Xinying Jia

    (The University of Queensland)

  • Irina Vetter

    (The University of Queensland
    The University of Queensland)

  • Derek R. Laver

    (University of Newcastle)

  • Bradley S. Launikonis

    (The University of Queensland)

  • Angela Dulhunty

    (Australian National University)

  • Eivind A. B. Undheim

    (The University of Queensland
    University of Oslo)

  • Mehdi Mobli

    (The University of Queensland)

Abstract

Multivalent ligands of ion channels have proven to be both very rare and highly valuable in yielding unique insights into channel structure and pharmacology. Here, we describe a bivalent peptide from the venom of Xibalbanus tulumensis, a troglobitic arthropod from the enigmatic class Remipedia, that causes persistent calcium release by activation of ion channels involved in muscle contraction. The high-resolution solution structure of φ-Xibalbin3-Xt3a reveals a tandem repeat arrangement of inhibitor-cysteine knot (ICK) domains previously only found in spider venoms. The individual repeats of Xt3a share sequence similarity with a family of scorpion toxins that target ryanodine receptors (RyR). Single-channel electrophysiology and quantification of released Ca2+ stores within skinned muscle fibers confirm Xt3a as a bivalent RyR modulator. Our results reveal convergent evolution of RyR targeting toxins in remipede and scorpion venoms, while the tandem-ICK repeat architecture is an evolutionary innovation that is convergent with toxins from spider venoms.

Suggested Citation

  • Michael J. Maxwell & Chris Thekkedam & Cedric Lamboley & Yanni K.-Y. Chin & Theo Crawford & Jennifer J. Smith & Junyu Liu & Xinying Jia & Irina Vetter & Derek R. Laver & Bradley S. Launikonis & Angela, 2023. "A bivalent remipede toxin promotes calcium release via ryanodine receptor activation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36579-w
    DOI: 10.1038/s41467-023-36579-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36579-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36579-w?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. Erhu Cao & Maofu Liao & Yifan Cheng & David Julius, 2013. "TRPV1 structures in distinct conformations reveal activation mechanisms," Nature, Nature, vol. 504(7478), pages 113-118, December.
    2. Eivind A. B. Undheim & Ronald A. Jenner, 2021. "Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Kellie A. Woll & Omid Haji-Ghassemi & Filip Van Petegem, 2021. "Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM," Nature Communications, Nature, vol. 12(1), pages 1-13, 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. Wai Lok So & Wenyan Nong & Yichun Xie & Tobias Baril & Hai-yao Ma & Zhe Qu & Jasmine Haimovitz & Thomas Swale & Juan Diego Gaitan-Espitia & Kwok Fai Lau & Stephen S. Tobe & William G. Bendena & Zhen-p, 2022. "Myriapod genomes reveal ancestral horizontal gene transfer and hormonal gene loss in millipedes," Nature Communications, Nature, vol. 13(1), pages 1-12, 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. Robyn T. Rebbeck & Bengt Svensson & Jingyan Zhang & Montserrat Samsó & David D. Thomas & Donald M. Bers & Razvan L. Cornea, 2024. "Kinetics and mapping of Ca-driven calmodulin conformations on skeletal and cardiac muscle ryanodine receptors," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    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. Arthur Neuberger & Kirill D. Nadezhdin & Alexander I. Sobolevsky, 2021. "Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    8. Marco C. Miotto & Steven Reiken & Anetta Wronska & Qi Yuan & Haikel Dridi & Yang Liu & Gunnar Weninger & Carl Tchagou & Andrew R. Marks, 2024. "Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. 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.
    10. 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.
    11. 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.
    12. Takuya Kobayashi & Akihisa Tsutsumi & Nagomi Kurebayashi & Kei Saito & Masami Kodama & Takashi Sakurai & Masahide Kikkawa & Takashi Murayama & Haruo Ogawa, 2022. "Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:14:y:2023:i:1:d:10.1038_s41467-023-36579-w. 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.