Cytolytic and K+ channel blocking activities of β-KTx and scorpine-like peptides purified from scorpion venoms

Among the scorpion venom components whose function are poorly known or even show contrasting pharmacological results are those called "orphan peptides". The most widely distributed are named beta-KTx or scorpine-like peptides. They contain three disulfide bridges with two recognizable domains: a freely moving N-terminal amino acid sequence and a tightly folded C-terminal region with a cysteine-stabilized alpha/beta (CS-alpha beta) motif. Four such peptides and three cloned genes are reported here. They were assayed for their cytolytic, antimicrobial and K+ channel-blocking activities. Two main characteristics were found: the existence of an unusual structural and functional diversity, whereby the full-length peptide can lyse cells or kill microorganisms, and a C-terminal domain containing the CS-alpha beta motif that can block K+ channels. Furthermore, sequence analyses and phylogenetic reconstructions are used to discuss the evolution of this type of peptide and to highlight the versatility of the CS-alpha beta structures.