We have located links that may give you full text access.
Not Goanna Get Me: Mutations in the Savannah Monitor Lizard (Varanus exanthematicus) Nicotinic Acetylcholine Receptor Confer Reduced Susceptibility to Sympatric Cobra Venoms.
Neurotoxicity Research 2021 August
Antagonistic coevolutionary relationships provide intense selection pressure which drive changes in the genotype. Predator-prey interactions have caused some venomous snakes and their predators/prey to evolve α-neurotoxin resistance through changes at the orthosteric site of nicotinic acetylcholine receptors. The presence of negatively charged amino acids at orthosteric site positions 191 and 195 is the ancestral state. These negatively charged amino acids have exerted a selection pressure for snake venom α-neurotoxins to evolve with strong positive charges on their molecular surface, with the opposite-charge attraction facilitating the binding by the neurotoxins. We aimed to test the effects of a series of mutations whereby one or both negatively charged amino acids are replaced by uncharged residues to ascertain if this was a novel form of reduced venom susceptibility in the varanid species. Using a biolayer interferometry assay, we tested the relative binding of α-neurotoxin-rich snake venoms against the orthosteric sites of V. giganteus (Perentie) and V. komodoensis (Komodo dragon), which both possess the negatively charged aspartic acid at position 191; V. mertensi (Merten's water monitor), which also has aspartic acid at position 195; and Varanus exanthematicus (savannah monitor), which lacks negatively charged amino acids at both positions 191 and 195. The orthosteric sites of these species are otherwise identical. In order to complete the structure-function relationship examination, we also tested a mutant version with the negatively charged aspartic acid at both positions 191 and 195. It was demonstrated that the presence of a negatively charged amino acid at either position 191 or 195 is crucial for the successful binding of snake venom α-neurotoxins, with V. giganteus, V. komodoensis and V. mertensi all strongly bound. The mutant version containing a negatively charged amino acid at both positions was bound equipotently to the native forms of V. giganteus, V. komodoensis and V. mertensi. Thus, the presence of a negatively charged amino acid at both positions does not increase binding affinity. In contrast, Varanus exanthematicus, lacking a negatively charged amino acid at either position, displayed dramatically less sensitivity to neurotoxins compared with the other species. V. exanthematicus is distinguished from the other species examined in this study by being a small, terrestrial, slow-moving species living sympatrically with a high density of large cobra species that have neurotoxin-rich venoms. Thus, this vulnerable prey item seems to have evolved a novel form of reduced susceptibility to snake venom neurotoxins under a strong selection pressures from these neurotoxic predators. These results therefore contribute to the body of knowledge of predator/prey chemical arm races while providing novel insights into the structure-activity relationships of the orthosteric site of the nicotinic acetylcholine receptor alpha-subunit.
Full text links
Related Resources
Trending Papers
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.Pharmaceuticals 2024 March 27
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app