BcsTx3 is a founder of a novel sea anemone toxin family of potassium channel blocker

Sea anemonevenoms have become a rich source of peptide toxins which are invaluable tools for studying the structure and functions of ion channels. In this work, BcsTx3, a toxin found in the venom of a Bunodosomacaissarum (population captured at the Saint Peter and Saint Paul Archipelago, Brazil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage-gated potassium channels(KV1.1–KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERGand ShakerIR) and three cloned voltage-gated sodium channelisoforms (NaV1.2, NaV1.4and BgNaV1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila ShakerIR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on NaV channels. Biochemical characterization reveals that BcsTx3 is a 50 amino acid peptide crosslinked by four disulfide bridges, and sequence comparison allowed BcsTx3 to be classified as a novel type of sea anemonetoxin acting on KV channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family.