Heterodimeric Insecticidal Peptide Provides New Insights into the Molecular and Functional Diversity of Ant Venoms

Axel Touchard; Helen C Mendel; Isabelle Boulogne; Volker Herzig; Nayara Braga Emidio; Glenn F King; Mathilde Triquigneaux; Lucie Jaquillard; Rémy Beroud; Michel De Waard; Olivier Delalande; Alain Dejean; Markus Muttenthaler; Christophe Duplais

doi:10.1021/acsptsci.0c00119

Back

Heterodimeric Insecticidal Peptide Provides New Insights into the Molecular and Functional Diversity of Ant Venoms

Journal article

Peer reviewed

Heterodimeric Insecticidal Peptide Provides New Insights into the Molecular and Functional Diversity of Ant Venoms

Axel Touchard, Helen C Mendel, Isabelle Boulogne, Volker Herzig, Nayara Braga Emidio, Glenn F King, Mathilde Triquigneaux, Lucie Jaquillard, Rémy Beroud, Michel De Waard, …

ACS Pharmacology & Translational Science, Vol.3(6), pp.1211-1224

2020

DOI: https://doi.org/10.1021/acsptsci.0c00119

PMCID: PMC7737211

PMID: 33344898

Files and links (1)

url

https://doi.org/10.1021/acsptsci.0c00119View

Published Version

Abstract

heterodimeric toxin

disulfide bond

insecticide properties

cytotoxicity

ant venom

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 (t 1/2 = 13 h) than its homodimers or monomers (t 1/2 < 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.

Details

Title: Heterodimeric Insecticidal Peptide Provides New Insights into the Molecular and Functional Diversity of Ant Venoms
Authors: Axel Touchard (Author) - Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Helen C Mendel (Author) - The University of Queensland
Isabelle Boulogne (Author) - Université de Rouen Normandie
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, GeneCology Research Centre - Legacy
Nayara Braga Emidio (Author) - The University of Queensland
Glenn F King (Author) - The University of Queensland
Mathilde Triquigneaux (Author) - Smartox Biotechnology
Lucie Jaquillard (Author) - Smartox Biotechnology
Rémy Beroud (Author) - Smartox Biotechnology
Michel De Waard (Author) - Nantes Université
Olivier Delalande (Author) - Université de Rennes
Alain Dejean (Author) - Université de Toulouse
Markus Muttenthaler (Author) - The University of Queensland
Christophe Duplais (Author) - Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Publication details: ACS Pharmacology & Translational Science, Vol.3(6), pp.1211-1224
Publisher: American Chemical Society
Date published: 2020
DOI: 10.1021/acsptsci.0c00119
ISSN: 2575-9108
PMID: 33344898; PMC7737211
Grants: Be(e) friendly venomous spiders! Novel biopesticides from arachnid venoms, FT190100482, Australian Research Council (Australia, Canberra) - ARC
Venoms to drugs: translating venom peptides into human therapeutics, 1136889, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Aquatic chemo-modulators: a novel source for potent molecular probes, DP190101667, Australian Research Council (Australia, Canberra) - ARC
Grant note: This work was supported by Investissement d’Avenir of the Agence National de la Recherche (CEBA: ANR-10-LABX-25-01). M.D.W. acknowledges financial support from ANR-11-LABX-0015. M.M. was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program (714366). The Vienna Science and Technology Fund (WWTF; LS18-053).
Organisation Unit: School of Science and Engineering - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99498107302621
Output Type: Journal article

Metrics

26 Record Views

9 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Chemistry, Medicinal; Pharmacology & Pharmacy

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: SDGs from InCites