Mipartoxin-I, a novel three-finger toxin, is the major neurotoxic component in the venom of the redtail coral snake Micrurus mipartitus (Elapidae)

Abstract

The major venom component of Micrurus mipartitus, a coral snake distributed from Nicaragua to northern South America, was characterized biochemically and functionally. This protein, named mipartoxin-I, is a novel member of the three-finger toxin superfamily, presenting the characteristic cysteine signature and amino acid sequence length of the short-chain, type-I, α-neurotoxins. Nevertheless, it varies considerably from related toxins, with a sequence identity not higher than 70% in a multiple alignment of 67 proteins within this family. Its observed molecular mass (7030.0) matches the value predicted by its amino acid sequence, indicating lack of post-translational modifications. Mipartoxin-I showed a potent lethal effect in mice (intraperitoneal median lethal dose: 0.06 μg/g body weight), and caused a clear neuromuscular blockade on both avian and mouse nerve-muscle preparations, presenting a post-synaptic action through the cholinergic nicotinic receptor. Since mipartoxin-I is the most abundant (28%) protein in M. mipartitus venom, it should play a major role in its toxicity, and therefore represents an important target for developing a therapeutic antivenom, which is very scarce or even unavailable in the regions where this snake inhabits. The structural information here provided might help in the preparation of a synthetic or recombinant immunogen to overcome the limited venom availability.

Neuromuscular Activity of Micrurus laticollaris (Squamata: Elapidae) Venom in Vitro

“…Figure 3A shows a representative record of the neuromuscular blockade caused by a venom concentration of 10 µg/mL and contracture responses to ACh and KCl before and after venom treatment. The decrease of the twitch tension in avian neuromuscular preparations caused by Elapidic venoms has been previously shown [13,21,22,23,24,25]. At these preparations, the muscle-type nicotinic receptors are distributed alongside the muscle fiber characterizing the multiple neuromuscular junctions [26].…”

Maintenance of red-tail coral snake (Micrurus mipartitus) in captivity and evaluation of individual venom variability

“…According to Rey-Suárez et al (2012) this peak corresponds to the "Mipartoxin", a three-finger type toxin that showed high lethality. It would be important to determine if the venom lethality of this specimen may be lower in relation to the other specimens.…”

“…Therefore, it is necessary to evaluate alternatives to standardize protocols for the maintenance of these species in captivity. The scope of this study is to evaluate different approaches on captive maintenance and characterize the individual variability of venom in adult individuals of Micrurus mipartitus, since there is little knowledge on the venom composition and action for this species and the importance of producing specific antivenoms (Rey-Suárez et al, 2011;Rey-Suárez et al, 2012, Renjifo et al, 2012.…”

Snakebites in Colombia

“…and Pelamis platurus venoms is the postsynaptic blockade by competitive inhibition of acetylcholine (a-neurotoxins). This group of toxins belongs to the three-finger toxin superfamily (3FTx) (Otero 2007(Otero , 2014Rey-Suárez et al 2012;Da Silva and Bucaretchi 2003;Brazil 1987;Mori et al 1989). The venom of M. dissoleucus from Colombia also has postsynaptic action combined with myotoxic effect (Renjifo et al 2012), the latter being similar to that previously described for M. mipartitus venom from Colombia (Otero et al 1992b).…”

“…venoms are of low ability to induce edema, hemorrhage, and proteolysis, but they are indirectly hemolytic and some of them are myotoxic (Otero et al 1992b;Gutiérrez et al 1980a;Rey-Suárez et al 2012). The latter effect was then documented in human bites inflicted by M. fulvius in the USA and M. laticollaris from Mexico (Kitchens and Van Mierop 1987;Pettigrew and Glass 1985) and by coral snakes from the Amazonian region in Colombia (Otero- Patiño 2007Patiño , 2011Otero 2007), as it was also described for M. lemniscatus in Peru (Manock et al 2008).…”