Functional evolution of scorpion venom peptides with an inhibitor cystine knot fold.

摘要: The ICK (inhibitor cystine knot) defines a large superfamily of polypeptides with high structural stability and functional diversity. Here, we describe new scorpion venom-derived K+ channel toxin (named λ-MeuKTx-1) an fold through gene cloning, chemical synthesis, nuclear magnetic resonance spectroscopy, Ca2+ release measurements electrophysiological recordings. λ-MeuKTx-1 was found to adopt that contains three-strand anti-parallel β-sheet 310-helix. Functionally, this peptide selectively inhibits the Drosophila Shaker but is not capable activating skeletal-type channels/ryanodine receptors, which remarkably different from previously known venom peptides. removal two C-terminal residues led loss inhibitory activity on channel, whereas amidation resulted in emergence four mammalian channels accompanied by channel. A combination pharmacological data allows recognition three putative sites involved blockade λ-MeuKTx-1. presence dyad supports convergence among peptides folds. Furthermore, similarities precursor organization, exon-intron structure, 3D-fold function suggest ICK-type inhibitors activators share common ancestor their divergence occurs after speciation between buthidae non-buthids. characterizations first channel-blocking sheds light functionally divergent convergent evolution conserved scaffold ancient origin.