The Toxins Purified from Tityus Serrulatus (Lutz & Mello)Venom

Abstract

The toxicity of Tityus serrulatus venom is mainly due to a complex mixture of basic proteins of low molecular weight (MW< 8000 Da) which are active on the voltage-sensitive Na⁺ channel of excitable cells. One group of toxins, the α-toxins, delays inactivation of the Na⁺ channel. A second group, the β- toxins, produces a transient shift in the voltage-dependence of Na⁺ channel activation and increases the tendency of the cells to fire repetitively. The two groups bind specifically to two different binding sites, sites 3 and 4, of Na⁺ channels present in rat brain synaptosomes. The primary structure of the main toxins has been determined and consists of a single amino acid chain of 61 to 66 residues cross-linked by four disulfide bridges. Some secondary structural elements have also been determined. More recently, using molecular biological techniques, cDNAs encoding the precursors of α and β-toxins have been cloned from a cDNA library of Tityus serrulatus venom gland. The precursors contain a signal peptide of about 20 – 22 residues, the mature toxin and three additional Gly-Lys-Lys residues at the C-terminal that are not present in the mature toxins. The Lys residues are removed by a carboxypeptidase and the remaining Gly-extended peptides are converted into α-amidated C-terminal toxins. Toxins active at K⁺ channels have also been purified from Tityus serrulatus venom. At present, only two toxins have been characterized, namely a short polypeptide of 37 amino acid residues cross-linked by three disulfide bridges that competes for 125I-alpha DTX (dendrotoxin) binding sites in synaptic membranes, and a longer nonhomologous toxin of 8 016 Da, whose primary structure has only been determined at the level of its NH2 terminal.