Molecular cloning and characterization of four scorpion K +-toxin-like peptides: A new subfamily of venom peptides (α-KTx14) and genomic analysis of a member

Abstract

Four full-length cDNAs encoding the precursors of four K +-toxin-like peptides (named BmKK 1, BmKK 2, BmKK 3 and BmmKK 4, respectively) were first isolated from a venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch. The deduced precursors of BmKK 1, BmKK 2 and BmKK 3 are all made of 54 amino acid residues including a signal peptide of 23 residues, and a mature toxin of 31 residues with three disulfide bridges. The precursor of BmKK 4 is composed of 55 amino acid residues including a signal peptide of 23 residues, a mature toxin of 30 residues cross-linked by three disulfide bridges, and an extra Gly-Lys tail which should be removed in the processing step. The four peptides displayed 24–97% sequence identity with each other, and less than 27% homology with any other scorpion toxins described. However, they shared a common disulfide bridge pattern, which was consistent with that of most short-chain K +-toxins, suggesting they represent a new class of scorpion toxins and their target receptors may be a subfamily of K + channels. We classified the BmKK toxin subfamily as alpha-KTx14 according to the classification rules. The genomic sequence of BmKK 2 was also cloned and sequenced. It consisted of two exons, disrupted by an intron of 79 bp inserted in the region encoding the C-terminal part of the signal peptide. This structure was very similar to that of other K +-toxins described previously.