Heterodimeric Insecticidal Peptide Provides New Insights into the Molecular and Functional Diversity of Ant Venoms
Year: 2020
Type: article
Abstract: Ants use venom for predation, defense, and communication; however, the molecular diversity, function, and potential applications of ant venom remains understudied compared to other venomous lineages such as arachnids, snakes and cone snails. In this work, we used a multidisciplinary approach that encompassed field work, proteomics, sequencing, chemical synthesis, structural analysis, molecular modeling, stability studies, and in vitro and in vivo bioassays to investigate the molecular diversity of the venom of the Amazonian Pseudomyrmex penetrator ants. We isolated a potent insecticidal heterodimeric peptide Δ-pseudomyrmecitoxin-Pp1a (Δ-PSDTX-Pp1a) composed of a 27-residue long A-chain and a 33-residue long B-chain cross-linked by two disulfide bonds in an antiparallel orientation. We chemically synthesized Δ-PSDTX-Pp1a, its corresponding parallel AA and BB homodimers, and its monomeric chains and demonstrated that Δ-PSDTX-Pp1a had the most potent insecticidal effects in blowfly assays (LD50 = 3 nmol/g). Molecular modeling and circular dichroism studies revealed strong α-helical features, indicating its cytotoxic effects could derive from cell membrane pore formation or disruption. The native heterodimer was substantially more stable against proteolytic degradation (t1/2 = 13 h) than its homodimers or monomers (t1/2 < 20 min), indicating an evolutionary advantage of the more complex structure. The proteomic analysis of Pseudomyrmex penetrator venom and in-depth characterization of Δ-PSDTX-Pp1a provide novel insights in the structural complexity of ant venom and further exemplifies how nature exploits disulfide-bond formation and dimerization to gain an evolutionary advantage via improved stability, a concept that is highly relevant for the design and development of peptide therapeutics, molecular probes, and bioinsecticides.
Institutions: Centre National de la Recherche Scientifique, Centre de Coopération Internationale en Recherche Agronomique pour le Développement, AgroParisTech, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Ecologie des Forêts de Guyane, Université des Antilles et de la Guyane, Université des Antilles, The University of Queensland, Institute for Molecular Bioscience, Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale, Université de Rouen Normandie, University of the Sunshine Coast, Inserm, Institut du Thorax, Laboratoire d'Excellence Canaux Ioniques d'Intérêt Thérapeutique, Université de Nantes, Nantes Université, Institut de génétique et de développement de Rennes, Université de Rennes, Université Toulouse III - Paul Sabatier, Ecolab (United Kingdom), Institut National Polytechnique de Toulouse, Laboratoire Écologie Fonctionnelle et Environnement, Ecolab (France), Université de Toulouse, University of Vienna
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1023714513, NExT (I-SITE), G1517818289, G2187564931, G294214751, G311888100, Canaux ioniques d'intérêt thérapeutique, CEnter of the study of Biodiversity in Amazonia, G434337789, Novel therapeutic approaches to improve gastrointestinal wound healing, G7240651115, Targeting mucosal biofilms in patients with gastrointestinal disorders, Aquatic chemo-modulators: a novel source for potent molecular probes
OpenAlex ID: W3092380078