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
Affiliations
Samuel D. Robinson
Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; Corresponding author
Lucas Kambanis
School of Chemistry, The University of Sydney, Camperdown, NSW 2006, Australia
Daniel Clayton
School of Chemistry, The University of Sydney, Camperdown, NSW 2006, Australia
Hannes Hinneburg
Department of Molecular Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
Leo Corcilius
School of Chemistry, The University of Sydney, Camperdown, NSW 2006, Australia
Alexander Mueller
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Andrew A. Walker
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Angelo Keramidas
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Sameer S. Kulkarni
School of Chemistry, The University of Sydney, Camperdown, NSW 2006, Australia
Alun Jones
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Irina Vetter
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
Morten Thaysen-Andersen
Department of Molecular Sciences, Macquarie University, Macquarie Park, NSW 2109, Australia
Richard J. Payne
School of Chemistry, The University of Sydney, Camperdown, NSW 2006, Australia; ARC Centre of Excellence for Innovations in Peptide and Protein Science, St Lucia, Australia
Glenn F. King
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; ARC Centre of Excellence for Innovations in Peptide and Protein Science, St Lucia, Australia
Eivind A.B. Undheim
Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia; Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway; Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, The University of Oslo, 0316 Oslo, Norway; Corresponding author
Summary: 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.
