Bcs T x3 is a founder of a novel sea anemone toxin family of potassium channel blocker

Sea anemone venoms 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 B unodosoma caissarum (population captured at the S aint P eter and S aint P aul A rchipelago, B razil) was purified and biochemically and pharmacologically characterized. The pharmacological effects were studied on 12 different subtypes of voltage‐gated potassium channels (K V 1.1–K V 1.6; K V 2.1; K V 3.1; K V 4.2; K V 4.3; h ERG and Shaker IR) and three cloned voltage‐gated sodium channel isoforms (Na V 1.2, Na V 1.4 and BgNa V 1.1) expressed in X enopus laevis oocytes. BcsTx3 shows a high affinity for D rosophila S haker IR channels over rKv1.2, hKv1.3 and rKv1.6, and is not active on Na V 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 anemone toxin acting on K V channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family.