A pain-causing and paralytic ant venom glycopeptide

Samuel D. Robinson*, Lucas Kambanis, Daniel Clayton, Hannes Hinneburg, Leo Corcilius, Alexander Mueller, Andrew A. Walker, Angelo Keramidas, Sameer S. Kulkarni, Alun Jones, Irina Vetter, Morten Thaysen-Andersen, Richard J. Payne, Glenn F. King, Eivind A. B. Undheim*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)
    37 Downloads (Pure)

    Abstract

    Ants (Hymenoptera: Formicidae) are familiar inhabitants of most terrestrial environments. Although we are aware of the ability of many species to sting, knowledge of ant venom chemistry remains limited. Herein, we describe the discovery and characterization of an O-linked glycopeptide (Mg7a) as a major component of the venom of the ant Myrmecia gulosa. Electron transfer dissociation and higher-energy collisional dissociation tandem mass spectrometry were used to localize three α-N-acetylgalactosaminyl residues (α-GalNAc) present on the 63-residue peptide. To allow for functional studies, we synthesized the full-length glycosylated peptide via solid-phase peptide synthesis, combined with diselenide–selenoester ligation-deselenization chemistry. We show that Mg7a is paralytic and lethal to insects, and triggers pain behavior and inflammation in mammals, which it achieves through a membrane-targeting mode of action. Deglycosylation of Mg7a renders it insoluble in aqueous solution, suggesting a key solubilizing role of the O-glycans.

    Original languageEnglish
    Article number103175
    Pages (from-to)1-20
    Number of pages20
    JournaliScience
    Volume24
    Issue number10
    Early online date25 Sept 2021
    DOIs
    Publication statusPublished - 22 Oct 2021

    Bibliographical note

    Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • Natural product chemistry
    • Biomolecules
    • Neuroscience

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