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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
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    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
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