New weak toxins from the cobra venom

Starkov, Vladislav G.; Polyak, Ya. L.; Vulfius, E. A.; Kryukova, Elena V.; Tsetlin, Victor I.; Utkin, Yuri N.

doi:10.1134/s1068162009010026

Cited by 5 publications

(3 citation statements)

References 32 publications

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“…Potent α-neurotoxicity preceded the evolution of the high-pressure front-fanged system of elapids, as was revealed by our discovery of α-colubritoxin, the first 3FTx isolated and characterized from a non-front-fanged lineage [59]. The toxin was of the same form as had been studied in elapid snakes previously, where they had been called ‘weak neurotoxins’ since they were only weakly potent on mice [137,138,139,140,141,142,143,144,145,146,147,148,149]. A problem that had also confounded studies of Boiga irregularis (brown tree snake), which had thus concluded they were non-venomous based on their effects in a murine model [150,151,152,153,154,155].…”

Section: Resultsmentioning

confidence: 99%

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Yang

Deuis

Dashevsky

et al. 2016

Toxins

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Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes. A spectacular point on the venom system continuum is the long-glanded blue coral snake (Calliophis bivirgatus), a specialist feeder that preys on fast moving, venomous snakes which have both a high likelihood of prey escape but also represent significant danger to the predator itself. The maxillary venom glands of C. bivirgatus extend one quarter of the snake’s body length and nestle within the rib cavity. Despite the snake’s notoriety its venom has remained largely unstudied. Here we show that the venom uniquely produces spastic paralysis, in contrast to the flaccid paralysis typically produced by neurotoxic snake venoms. The toxin responsible, which we have called calliotoxin (δ-elapitoxin-Cb1a), is a three-finger toxin (3FTx). Calliotoxin shifts the voltage-dependence of NaV1.4 activation to more hyperpolarised potentials, inhibits inactivation, and produces large ramp currents, consistent with its profound effects on contractile force in an isolated skeletal muscle preparation. Voltage-gated sodium channels (NaV) are a particularly attractive pharmacological target as they are involved in almost all physiological processes including action potential generation and conduction. Accordingly, venom peptides that interfere with NaV function provide a key defensive and predatory advantage to a range of invertebrate venomous species including cone snails, scorpions, spiders, and anemones. Enhanced activation or delayed inactivation of sodium channels by toxins is associated with the extremely rapid onset of tetanic/excitatory paralysis in envenomed prey animals. A strong selection pressure exists for the evolution of such toxins where there is a high chance of prey escape. However, despite their prevalence in other venomous species, toxins causing delay of sodium channel inhibition have never previously been described in vertebrate venoms. Here we show that NaV modulators, convergent with those of invertebrates, have evolved in the venom of the long-glanded coral snake. Calliotoxin represents a functionally novel class of 3FTx and a structurally novel class of NaV toxins that will provide significant insights into the pharmacology and physiology of NaV. The toxin represents a remarkable case of functional convergence between invertebrate and vertebrate venom systems in response to similar selection pressures. These results underscore the dynamic evolution of the Toxicofera re...

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Section: Resultsmentioning

confidence: 99%

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Yang

Deuis

Dashevsky

et al. 2016

Toxins

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“…WTX, ␣-Ctx, and NT II were obtained as described previously (23)(24)(25) and OWT as described previously (26). NT I was obtained as described previously (27) with additional purification by reversed phase HPLC.…”

Section: Methodsmentioning

confidence: 99%

Neurotoxins from Snake Venoms and α-Conotoxin ImI Inhibit Functionally Active Ionotropic γ-Aminobutyric Acid (GABA) Receptors

Kudryavtsev

Shelukhina

Son

et al. 2015

Journal of Biological Chemistry

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Background: Different snake venom three-finger toxins interact with various receptors, channels, and membranes. Results: Here, we demonstrate that GABA A receptors are inhibited by ␣-cobratoxin, other long chain ␣-neurotoxins, nonconventional toxin from Naja kaouthia, and ␣-conotoxin ImI. Conclusion: Some toxin blockers of nicotinic acetylcholine receptors also inhibit GABA A receptors. Significance: Three-finger toxins offer new scaffolds for the design of GABA A receptor effectors.

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“…This toxin was considered a novel long chain 3FTx, because of its reversible antagonistic effect on muscle-type and weaker but also on neuronal α7 nAChR. In other similar toxins, the activity is commonly almost or totally irreversible [ 56 ]. As in the subgroup 2-A, sequences from subgroup 2-B are differentiated by the presence of a fifth extra disulfide bridge located in the finger I, as found in Candoxin.…”

Section: Discussionmentioning

confidence: 99%

Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

Kleiz-Ferreira

Cirauqui

Trajano

et al. 2021

Toxins

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Studies on 3FTxs around the world are showing the amazing diversity in these proteins both in structure and function. In Brazil, we have not realized the broad variety of their amino acid sequences and probable diversified structures and targets. In this context, this work aims to conduct an in silico systematic study on available 3FTxs found in Micrurus species from Brazil. We elaborated a specific guideline for this toxin family. First, we grouped them according to their structural homologue predicted by HHPred server and further curated manually. For each group, we selected one sequence and constructed a representative structural model. By looking at conserved features and comparing with the information available in the literature for this toxin family, we managed to point to potential biological functions. In parallel, the phylogenetic relationship was estimated for our database by maximum likelihood analyses and a phylogenetic tree was constructed including the homologous 3FTx previously characterized. Our results highlighted an astonishing diversity inside this family of toxins, showing some groups with expected functional similarities to known 3FTxs, and pointing out others with potential novel roles and perhaps structures. Moreover, this classification guideline may be useful to aid future studies on these abundant toxins.

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New weak toxins from the cobra venom

Cited by 5 publications

References 32 publications

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

The Snake with the Scorpion’s Sting: Novel Three-Finger Toxin Sodium Channel Activators from the Venom of the Long-Glanded Blue Coral Snake (Calliophis bivirgatus)

Neurotoxins from Snake Venoms and α-Conotoxin ImI Inhibit Functionally Active Ionotropic γ-Aminobutyric Acid (GABA) Receptors

Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

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