- Title
- A bivalent remipede toxin promotes calcium release via ryanodine receptor activation
- Creator
- Maxwell, Michael J.; Thekkedam, Chris; Launikonis, Bradley S.; Dulhunty, Angela; Undheim, Eivind A. B.; Mobli, Mehdi; Lamboley, Cedric; Chin, Yanni K.-Y.; Crawford, Theo; Smith, Jennifer J.; Liu, Junyu; Jia, Xinying; Vetter, Irina; Laver, Derek R.
- Relation
- Nature Communications Vol. 14, Issue 1, no. 1036
- Publisher Link
- http://dx.doi.org/10.1038/s41467-023-36579-w
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2023
- Description
- 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.
- Subject
- bivalent; calcium; remipede; toxin
- Identifier
- http://hdl.handle.net/1959.13/1479765
- Identifier
- uon:50369
- Identifier
- ISSN:2041-1723
- Rights
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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