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Published VersionCC BY V4.0, Open Access
Journal article
The Target Selects the Toxin: Specific Amino Acids in Snake-Prey Nicotinic Acetylcholine Receptors That Are Selectively Bound by King Cobra Venoms
Toxins, Vol.14(8), pp.1-12
2022
PMID: 36006190
Abstract
Snake venom is an adaptive ecological trait that has evolved primarily as a form of prey subjugation. Thus, the selection pressure for toxin diversification is exerted by the prey’s physiological targets, with this pressure being particularly acute for specialist feeders, such as the King Cobra species, all of which are snake-prey specialists. However, while extensive research has been undertaken to elucidate key amino acids that guide toxin structure–activity relationships, reciprocal investigations into the specific sites guiding prey-lineage selective effects have been lacking. This has largely been due to the lack of assay systems amenable to systematic amino acid replacements of targeted proteins in the prey’s physiological pathways. To fill this knowledge gap, we used a recently described approach based upon mimotope peptides corresponding to the orthosteric site of nicotinic acetylcholine receptor alpha-1 subunits, a major binding site for snake venom neurotoxins that cause flaccid paralysis. We investigated the venoms of four different types of King Cobra (Cambodian, Javan, Malaysian, and Thai). This approach allowed for the determination of the key amino acid positions in King Cobra snake prey that are selectively bound by the toxins, whereby replacing these amino acids in the snake-prey orthosteric site with those from lizards or rats resulted in a significantly lower level of binding by the venoms, while conversely replacing the lizard or rat amino acids with those from the snake at that position increased the binding. By doing such, we identified three negatively charged amino acids in the snake orthosteric site that are strongly bound by the positively charged neurotoxic three-finger toxins found in King Cobra venom. This study, thus, sheds light on the selection pressures exerted by a specialist prey item for the evolution of lineage-selective toxins.
Details
- Title
- The Target Selects the Toxin: Specific Amino Acids in Snake-Prey Nicotinic Acetylcholine Receptors That Are Selectively Bound by King Cobra Venoms
- Authors
- Uthpala Chandrasekara (Author) - The University of QueenslandRichard Harris - The University of QueenslandBryan G Fry (Corresponding Author) - The University of Queensland
- Publication details
- Toxins, Vol.14(8), pp.1-12
- Publisher
- MDPI AG
- Date published
- 2022
- DOI
- 10.3390/toxins14080528
- ISSN
- 2072-6651
- PMID
- 36006190
- Copyright note
- © 2022 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 (https:// creativecommons.org/licenses/by/ 4.0/).
- Data Availability
- All data is shown in the figures.
- Grant note
- U.C. and R.J.H were supported by the University of Queensland International PhD scholarship fund.
- Organisation Unit
- Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991177844502621
- Output Type
- Journal article
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