Cargando…

It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula

Ant venoms have recently attracted increased attention due to their chemical complexity, novel molecular frameworks, and diverse biological activities. The heterodimeric peptide ∆-myrtoxin-Mp1a (Mp1a) from the venom of the Australian jack jumper ant, Myrmecia pilosula, exhibits antimicrobial, membra...

Descripción completa

Detalles Bibliográficos
Autores principales: Nixon, Samantha A., Dekan, Zoltan, Robinson, Samuel D., Guo, Shaodong, Vetter, Irina, Kotze, Andrew C., Alewood, Paul F., King, Glenn F., Herzig, Volker
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400207/
https://www.ncbi.nlm.nih.gov/pubmed/32629771
http://dx.doi.org/10.3390/biomedicines8070185
_version_ 1783566310111707136
author Nixon, Samantha A.
Dekan, Zoltan
Robinson, Samuel D.
Guo, Shaodong
Vetter, Irina
Kotze, Andrew C.
Alewood, Paul F.
King, Glenn F.
Herzig, Volker
author_facet Nixon, Samantha A.
Dekan, Zoltan
Robinson, Samuel D.
Guo, Shaodong
Vetter, Irina
Kotze, Andrew C.
Alewood, Paul F.
King, Glenn F.
Herzig, Volker
author_sort Nixon, Samantha A.
collection PubMed
description Ant venoms have recently attracted increased attention due to their chemical complexity, novel molecular frameworks, and diverse biological activities. The heterodimeric peptide ∆-myrtoxin-Mp1a (Mp1a) from the venom of the Australian jack jumper ant, Myrmecia pilosula, exhibits antimicrobial, membrane-disrupting, and pain-inducing activities. In the present study, we examined the activity of Mp1a and a panel of synthetic analogues against the gastrointestinal parasitic nematode Haemonchus contortus, the fruit fly Drosophila melanogaster, and for their ability to stimulate pain-sensing neurons. Mp1a was found to be both insecticidal and anthelmintic, and it robustly activated mammalian sensory neurons at concentrations similar to those reported to elicit antimicrobial and cytotoxic activity. The native antiparallel Mp1a heterodimer was more potent than heterodimers with alternative disulfide connectivity, as well as monomeric analogues. We conclude that the membrane-disrupting effects of Mp1a confer broad-spectrum biological activities that facilitate both predation and defense for the ant. Our structure–activity data also provide a foundation for the rational engineering of analogues with selectivity for particular cell types.
format Online
Article
Text
id pubmed-7400207
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-74002072020-08-23 It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula Nixon, Samantha A. Dekan, Zoltan Robinson, Samuel D. Guo, Shaodong Vetter, Irina Kotze, Andrew C. Alewood, Paul F. King, Glenn F. Herzig, Volker Biomedicines Article Ant venoms have recently attracted increased attention due to their chemical complexity, novel molecular frameworks, and diverse biological activities. The heterodimeric peptide ∆-myrtoxin-Mp1a (Mp1a) from the venom of the Australian jack jumper ant, Myrmecia pilosula, exhibits antimicrobial, membrane-disrupting, and pain-inducing activities. In the present study, we examined the activity of Mp1a and a panel of synthetic analogues against the gastrointestinal parasitic nematode Haemonchus contortus, the fruit fly Drosophila melanogaster, and for their ability to stimulate pain-sensing neurons. Mp1a was found to be both insecticidal and anthelmintic, and it robustly activated mammalian sensory neurons at concentrations similar to those reported to elicit antimicrobial and cytotoxic activity. The native antiparallel Mp1a heterodimer was more potent than heterodimers with alternative disulfide connectivity, as well as monomeric analogues. We conclude that the membrane-disrupting effects of Mp1a confer broad-spectrum biological activities that facilitate both predation and defense for the ant. Our structure–activity data also provide a foundation for the rational engineering of analogues with selectivity for particular cell types. MDPI 2020-06-30 /pmc/articles/PMC7400207/ /pubmed/32629771 http://dx.doi.org/10.3390/biomedicines8070185 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nixon, Samantha A.
Dekan, Zoltan
Robinson, Samuel D.
Guo, Shaodong
Vetter, Irina
Kotze, Andrew C.
Alewood, Paul F.
King, Glenn F.
Herzig, Volker
It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title_full It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title_fullStr It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title_full_unstemmed It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title_short It Takes Two: Dimerization Is Essential for the Broad-Spectrum Predatory and Defensive Activities of the Venom Peptide Mp1a from the Jack Jumper Ant Myrmecia pilosula
title_sort it takes two: dimerization is essential for the broad-spectrum predatory and defensive activities of the venom peptide mp1a from the jack jumper ant myrmecia pilosula
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400207/
https://www.ncbi.nlm.nih.gov/pubmed/32629771
http://dx.doi.org/10.3390/biomedicines8070185
work_keys_str_mv AT nixonsamanthaa ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT dekanzoltan ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT robinsonsamueld ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT guoshaodong ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT vetteririna ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT kotzeandrewc ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT alewoodpaulf ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT kingglennf ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula
AT herzigvolker ittakestwodimerizationisessentialforthebroadspectrumpredatoryanddefensiveactivitiesofthevenompeptidemp1afromthejackjumperantmyrmeciapilosula