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

Diego J.B. Orts*, Yehu Moran, Camila T. Cologna, Steve Peigneur, Bruno Madio, Daniela Praher, Loic Quinton, Edwin De Pauw, José E.P.W. Bicudo, Jan Tytgat, José C. De Freitas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 Bunodosoma caissarum (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; hERG and Shaker IR) and three cloned voltage-gated sodium channel isoforms (NaV1.2, NaV1.4 and BgNaV1.1) expressed in Xenopus laevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker IR 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 anemone toxin 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. We have demonstrated the biochemical and pharmacological characterization of a novel type of sea anemone KV-toxins. BcsTx3 is a peptidyl toxin with a unique sequence that acts potently upon Shaker IR channels through a pore blocking mechanism. Moreover, the distribution of this newly discovered type of KV-toxins among different actiniarian species suggests an ancient origin.

Original languageAmerican English
Pages (from-to)4839-4852
Number of pages14
JournalFEBS Journal
Volume280
Issue number19
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Bunodosoma caissarum
  • Saint Peter and Saint Paul Archipelago
  • potassium channel toxin
  • sea anemone
  • sequence alignment

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