A pain-causing and paralytic ant venom glycopeptide

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 geese. Electron transfer dissociation and higher-energy collisional dissociation tandem mass spectrometry were used to localize three alpha-N-acetylgalactosaminyl residues (alpha-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 diseleride-selenoester ligation-deselenization chemistry. We show that Mg7a is paralytic and lethal to insects, and trisers pain behavior and inflammation in mamrials, 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.

Automated summary

Ants are common inhabitants in terrestrial environments, and their venom chemistry, particularly the glycopeptide Mg7a, has been discovered and characterized. Mg7a exhibits paralytic and lethal effects on insects, as well as inducing pain and inflammation in mammals through a membrane-targeting mechanism. The presence of O-glycans plays a crucial role in the solubility of Mg7a in aqueous solutions.