Assessing the Binding of Venoms from Aquatic elapids to the Nicotinic Acetylcholine ReceptorOrthosteric Site of Different Prey Models

Richard Harris; Nicholas J Youngman; Christina N Zdenek; Tam M Huynh; Amanda Nouwens; Wayne C Hodgson; David Harrich; Nathan Dunstan; José A.  A Portes‑Junior; Bryan G Fry

doi:10.3390/ijms21197377

Back

Assessing the Binding of Venoms from Aquatic elapids to the Nicotinic Acetylcholine ReceptorOrthosteric Site of Different Prey Models

Journal article

Open access

Peer reviewed

Assessing the Binding of Venoms from Aquatic elapids to the Nicotinic Acetylcholine ReceptorOrthosteric Site of Different Prey Models

Richard Harris, Nicholas J Youngman, Christina N Zdenek, Tam M Huynh, Amanda Nouwens, Wayne C Hodgson, David Harrich, Nathan Dunstan, José A. A Portes‑Junior and Bryan G Fry

International Journal of Molecular Sciences, Vol.21(9), pp.1-13

2020

DOI: https://doi.org/10.3390/ijms21197377

PMID: 33036249

Files and links (1)

pdf

ijms-21-073779.11 MBDownload View

Published VersionCC BY V4.0, Open Access

Abstract

Elapidae

venom

neurotoxicity

nicotinic acetylcholine receptors

orthosteric

allosteric

The evolution of an aquatic lifestyle from land dwelling venomous elapids is a radical ecological modification, bringing about many evolutionary changes from morphology to diet. Diet is an important ecological facet which can play a key role in regulating functional traits such as venom composition and prey-specific targeting of venom. In addition to predating upon novel prey (e.g., fish, fish eggs and invertebrates), the venoms of aquatic elapids also face the challenge of increased prey-escape potential in the aquatic environment. Thus, despite the independent radiation into an aquatic niche on four separate occasions, the venoms of aquatic elapids are evolving under convergent selection pressures. Utilising a biolayer interferometry binding assay, this study set out to elucidate whether crude venoms from representative aquatic elapids were target-specific to the orthosteric site of postsynaptic nicotinic acetylcholine receptor mimotopes of fish compared to other terrestrial prey types. Representatives of the four aquatic lineages were: aquatic coral snakes representative was Micrurus surinamensis;, sea kraits representative was Laticauda colubrina; sea snakes representatives were two Aipysurus spp. and eight Hydrophis spp; and water cobras representative was Naja annulata. No prey-specific differences in crude venom binding were observed from any species tested, except for Aipysurus laevis, which showed slight evidence of prey-potency differences. For Hydrophis caerulescens, H. peronii, H. schistosus and M. surinamensis, there was a lack of binding to the orthosteric site of any target lineage. Subsequent testing on the in vitro chick-biventer cervicis muscle preparation suggested that, while the venoms of these species bound postsynaptically, they bound to allosteric sites rather than orthosteric. Allosteric binding is potentially a weaker but faster-acting form of neurotoxicity and we hypothesise that the switch to allosteric binding is likely due to selection pressures related to prey-escape potential. This research has potentially opened up the possibility of a new functional class of toxins which have never been assessed previously while shedding light on the selection pressures shaping venom evolution.

Details

Title: Assessing the Binding of Venoms from Aquatic elapids to the Nicotinic Acetylcholine ReceptorOrthosteric Site of Different Prey Models
Authors: Richard Harris - The University of Queensland
Nicholas J Youngman (Author) - The University of Queensland
Christina N Zdenek (Author) - The University of Queensland
Tam M Huynh (Author) - Monash University
Amanda Nouwens (Author) - The University of Queensland
Wayne C Hodgson (Author) - Monash University
David Harrich (Author) - QIMR Berghofer Medical Research Institute
Nathan Dunstan (Author) - Venom Supplies Pty Ltd (Australia)
José A. A Portes‑Junior (Author) - Instituto Butantan
Bryan G Fry (Corresponding Author) - The University of Queensland
Publication details: International Journal of Molecular Sciences, Vol.21(9), pp.1-13
Publisher: MDPI AG
Date published: 2020
DOI: 10.3390/ijms21197377
ISSN: 1422-0067; 1661-6596
PMID: 33036249
Copyright note: ©2020bythe 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/).
Grants: Functional evolution and therapeutic potential of snake venom coagulotoxins, DP190100304, Australian Research Council (Australia, Canberra) - ARC
Translational Venom and Antivenom Research, 1110343, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Grant note: R.J.H.: N.J.Y. and C.N.Z. was supported by the University of Queensland international and domestic PhD scholarship fund. JP was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (2018/25749-8).
Organisation Unit: Centre for Bioinnovation
Language: English
Record Identifier: 991177845002621
Output Type: Journal article

Metrics

1 Record Views

21 Times Cited - Web of Science

See more details

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: Biochemistry & Molecular Biology; Chemistry, Multidisciplinary

UN Sustainable Development Goals (SDGs)

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

Source: InCites