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

Author(s):Show less -

Orts, Diego J. B. ^[1] ; Moran, Yehu ^[2] ; Cologna, Camila T. ^[3] ; Peigneur, Steve ^[4] ; Madio, Bruno ^[1] ; Praher, Daniela ^[2] ; Quinton, Loic ^[3] ; De Pauw, Edwin ^[3] ; Bicudo, Jose E. P. W. ^[1] ; Tytgat, Jan ^[4] ; de Freitas, Jose C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Dept Physiol, BR-05508 Sao Paulo - Brazil

^[2] Univ Vienna, Fac Life Sci, Dept Mol Evolut & Dev, A-1010 Vienna - Austria

^[3] Univ Liege, Dept Chem, Lab Mass Spectrometry, B-4000 Liege - Belgium

^[4] Univ Leuven, Toxicol Lab, Louvain - Belgium

• Document type: Journal article
• Source: FEBS Journal; v. 280, n. 19, p. 4839-4852, OCT 2013.
• Web of Science Citations: 15

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 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 (K(V)1.1-K(V)1.6; K(V)2.1; K(V)3.1; K(V)4.2; K(V)4.3; hERG 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 Xenopuslaevis oocytes. BcsTx3 shows a high affinity for Drosophila Shaker 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. (AU)

• FAPESP's process: 11/21031-6 - Analysis of the mechanism of action involved in the selective activity of Abe III 1.3 in voltage-dependent K+ channels
• Grantee: Diego Jose Orts y Belato
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 09/07128-7 - Sea anemones neurotoxins as tools to study the physiology of voltage-gated potassium channels
• Grantee: Diego Jose Orts y Belato
• Support Opportunities: Scholarships in Brazil - Master