cDNAs encoding novel long-chain scorpion toxins (64 amino acid residues, including only six cysteines) were isolated from cDNA libraries produced from the venom glands of the scorpions Androctonus australis from Old World and Tityus serrulatus from New World. The encoded peptides were very similar to a recently identified toxin from T. serrulatus, which is active against the voltage-sensitive`delayed-rectifier' potassium channel, but they were completely different from the long-chain and short-chain scorpion toxins already characterised. However, there was some sequence similarity (42%) between these new toxins, Aa TX KL L and Ts TX KL L, and scorpion defensins purified from the hemolymph of Buthidae scorpions Leiurus quinquestriatus and A. australis. Thus, according to a multiple sequence alignment using CLUSTAL, these new toxins seem to be related to the scorpion defensins.z 1998 Federation of European Biochemical Societies.

A cDNA encoding the main T@II,F .wwhru.r ,%ncurotoxin was isolated from a venom gland cDNA library by using an oligonuclcotidc probe, The amino iICid scqucncr deduced I'rom the cDNA nucteotidc sequcncc indicated that the toxin is the processed product or a precursor containing:(i) a signal peptide of 20 residues: (ii) the amino acid sequence of the mature loxin: and (iii) an extra Gly-Lys-Lya tail al the C-terminal end before the termination codon. Thus, in addition to the remov;ll of the signal peptide by a signal pcptidasc, the generation of the mature toxin requires both a post-translational ClCUvagC by a carboxypcplidasc specific for basic rcsiducs and the XIion of an a-amidating enzyme. These results also show that the biosynthetic pathwuy for &toxins of"Ncw World' scorpion venoms is similar LO Ihat already described for a-toxins of 'Old World' scorpion venoms.

The venom of the scorpion, lltps serrulatus, was fractionated to investigate the chemical and pharmacological properties of its a-toxin content.Three a-toxins (Ts III, Ts IV and Ts V) were purified by conventional chromatography (gel filtration and ion-exchange chromatography), followed by immunoafhnity chromatography. Competition experiments using reference a-and/I-toxins suggested that these u-toxins were contaminated with around 0.01% of/I-toxin. The sequence of the first 30 amino acids of Ts IV was established. Using an oligonucleotide probe, a cDNA encoding its precursor was cloned from a venom gland cDNA library. The primary structure deduced from the cDNA nucleotide sequence provides possible explanations for the polymorphism of these three molecules.

No abstract

GABA A receptors shape synaptic transmission by modulating Cl − conductance across the cell membrane. Remarkably, animal toxins that specifically target GABA A receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABA A receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABA A receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α + /β − interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABA A receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.