A bivalent remipede toxin promotes calcium release via ryanodine receptor activation.

Autor: Maxwell MJ; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia., Thekkedam C; Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2601, Australia.; Developmental and Regenerative Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia., Lamboley C; School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Chin YK; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia., Crawford T; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia., Smith JJ; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia., Liu J; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia., Jia X; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia., Vetter I; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia.; School of Pharmacy, The University of Queensland, Woolloongabba, Australia., Laver DR; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, 2308, Australia., Launikonis BS; School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Dulhunty A; Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2601, Australia., Undheim EAB; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia. e.a.b.undheim@ibv.uio.no.; Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, 0316, Oslo, Norway. e.a.b.undheim@ibv.uio.no., Mobli M; Centre for Advanced Imaging, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.mobli@uq.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Feb 23; Vol. 14 (1), pp. 1036. Date of Electronic Publication: 2023 Feb 23.
DOI: 10.1038/s41467-023-36579-w
Abstrakt: 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 Ca 2+ 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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