TY - JOUR
T1 - Assessing the binding of venoms from aquatic elapids to the nicotinic acetylcholine receptor orthosteric site of different prey models
AU - Harris, Richard J.
AU - Youngman, Nicholas J.
AU - Zdenek, Christina N.
AU - Huynh, Tam M.
AU - Nouwens, Amanda
AU - Hodgson, Wayne C.
AU - Harrich, David
AU - Dunstan, Nathan
AU - Portes-Junior, José A.
AU - Fry, Bryan G.
N1 - Funding Information:
Funding: R.J.H.: N.J.Y. and C.N.Z. was supported by the University of Queensland international and domestic PhD scholarship fund. T.M.H. was supported by a PhD scholarship funded from an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence Grant (ID:1110343). B.G.F was funded by Australian Research Council Discovery Project DP190100304, JP was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (2018/25749-8).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
KW - Allosteric
KW - Elapidae
KW - Neurotoxicity
KW - Nicotinic acetylcholine receptors
KW - Orthosteric
KW - Venom
UR - http://www.scopus.com/inward/record.url?scp=85092254900&partnerID=8YFLogxK
U2 - 10.3390/ijms21197377
DO - 10.3390/ijms21197377
M3 - Article
C2 - 33036249
AN - SCOPUS:85092254900
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 19
M1 - 7377
ER -