New “Birtoxin analogs” from Androctonus australis venom

From the venom of the scorpion Androctonus australis, we have isolated a new bioactive polypeptide termed AaBTX-L1. When tested on the insect voltage-gated Na+ channel (para) of the fruit fly, this toxin was able to induce a clear shift in activation (V1/2), resulting in the opening of the channel at more negative membrane potentials. Furthermore, AaBTX-L1 was totally devoid of toxicity when injected into mice intracerebroventricularly and did not compete with radiolabeled voltage-gated K+ and Na+ channel toxins in binding experiments on rat brain synaptosomes. Using its N-terminal amino acid sequence to design degenerate primers, several clones were amplified by PCR from the A. australis venom gland cDNA library. As a consequence, seven full oligonucleotide sequences encoding “long-chain” polypeptides with only three disulfide bridges have been cloned for the first time and are described here. Remarkably, they share high similarity with the anti-insect toxin Birtoxin from Parabuthus transvaalicus.