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Bungarus multicinctus is a widely distributed and medically important elapid snake that produces lethal neurotoxic venom. To study and enhance existing antivenom, we explore the complete repertoire of its toxin genes based on de novo chromosome-level assembly and multi-tissue transcriptome data. Comparative genomic analyses suggest that the three-finger toxin family (3FTX) may evolve through the neofunctionalization of flanking LY6E. A long-neglected 3FTX subfamily (i.e., MKA-3FTX) is also investigated. Only one MKA-3FTX gene, which evolves a different protein conformation, is under positive selection and actively transcribed in the venom gland, functioning as a major toxin effector together with MKT-3FTX subfamily homologs. Furthermore, this lethal snake may acquire self-resistance to its β-bungarotoxin via amino acid replacements on fast-evolving KCNA2. This study provides valuable resources for further evolutionary and structure-function studies of snake toxins, which are fundamental for the development of effective antivenoms and drug candidates.
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http://dx.doi.org/10.1016/j.celrep.2022.111079 | DOI Listing |
Toxins (Basel)
July 2025
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
Three-finger toxins (3FTxs) are the largest group of nonenzymatic toxins found in snake venoms. Among them, neurotoxins that target nicotinic acetylcholine receptors are the most well-studied ligands. In addition to the classical neurotoxins, several other new classes have been characterized for their structure, receptor subtype, and species selectivity.
View Article and Find Full Text PDFToxins (Basel)
August 2025
Laboratório Bioquímica e Biofísica, Instituto Butantan, São Paulo 05503-900, Brazil.
, commonly known as the death adder, is a venomous Australian snake and a member of the Elapidae family. Due to its robust body and triangular head, it was historically misclassified as a viper. Its venom is known for neurotoxic, hemorrhagic, and hemolytic effects but displays low anticoagulant activity.
View Article and Find Full Text PDFBiochem Pharmacol
July 2025
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117558 Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600 Singapore; Department of Biochemistry, Medical College of Virginia, Vir
α-Neurotoxins, a prominent class of snake toxins belonging to the three-finger toxin (3FTx) superfamily, function as orthosteric antagonists of postsynaptic nicotinic acetylcholine receptors (nAChRs). Due to their high selectivity, α-neurotoxins have been widely used to characterize these physiologically important receptors. In this study, we investigated the concentration-response relationships of wild-type erabutoxin A (Ea), an α-neurotoxin, and six of its single-residue mutants by assessing their ability to inhibit acetylcholine-evoked currents mediated by α1β1γδ (fetal) and α1β1γε (adult) isoforms of human muscle-type nAChRs.
View Article and Find Full Text PDFToxins (Basel)
July 2025
Clinical Toxicology Research Group, University of Newcastle, Newcastle, NSW 2308, Australia.
The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder -one of the world's most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.
View Article and Find Full Text PDFProteomes
July 2025
Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto P.M.B. 2346, Nigeria.
Snake envenomation is a major public health issue in Nigeria, primarily due to bites from , , and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances.
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