Harris, Richard J., and Fry, Bryan G. (2021) Electrostatic resistance to alpha-neurotoxins conferred by charge reversal mutations in nicotinic acetylcholine receptors. Proceedings of the Royal Society of London Series B, Biological Sciences, 288 (1942). 20202703.

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Abstract

The evolution of venom resistance through coevolutionary chemical arms races has arisen multiple times throughout animalia. Prior documentation of resistance to snake venom α-neurotoxins consists of the N-glycosylation motif or the hypothesized introduction of arginine at positions 187 at the α-1 nicotinic acetylcholine receptor orthosteric site. However, no further studies have investigated the possibility of other potential forms of resistance. Using a biolayer interferometry assay, we first confirm that the previously hypothesized resistance conferred by arginine at position 187 in the honey badger does reduce binding to α-neurotoxins, which has never been functionally tested. We further discovered a novel form of α-neurotoxin resistance conferred by charge reversal mutations, whereby a negatively charged amino acid is replaced by the positively charged amino acid lysine. As venom α-neurotoxins have evolved strong positive charges on their surface to facilitate binding to the negatively charged α-1 orthosteric site, these mutations result in a positive charge/positive charge interaction electrostatically repelling the α-neurotoxins. Such a novel mechanism for resistance has gone completely undiscovered, yet this form of resistance has convergently evolved at least 10 times within snakes. These coevolutionary innovations seem to have arisen through convergent phenotypes to ultimately evolve a similar biophysical mechanism of resistance across snakes.

Item ID:	84133
Item Type:	Article (Research - C1)
ISSN:	1471-2954
Copyright Information:	© 2021 The Author(s) Published by the Royal Society. All rights reserved.
Date Deposited:	27 Jan 2025 23:14
FoR Codes:	31 BIOLOGICAL SCIENCES > 3104 Evolutionary biology > 310405 Evolutionary ecology @ 50% 31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310199 Biochemistry and cell biology not elsewhere classified @ 50%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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