Department of Physiology, Institute of Biosciences, University of São Paulo, Brazil.
FEBS J. 2013 Oct;280(19):4839-52. doi: 10.1111/febs.12456. Epub 2013 Aug 23.
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 (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 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 K(V) channels. Moreover, putative toxins homologous to BcsTx3 from two additional actiniarian species suggest an ancient origin of this newly discovered toxin family.
海葵毒液已成为肽毒素的丰富来源，这些毒素是研究离子通道结构和功能的宝贵工具。在这项工作中，从 Bunodosoma caissarum（在巴西圣彼得和圣保罗群岛捕获的种群）毒液中发现的 BcsTx3 被纯化并进行了生化和药理学表征。该毒素对 12 种不同亚型的电压门控钾通道（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 和 Shaker IR）以及三种克隆的电压门控钠通道亚型（Na(V)1.2、Na(V)1.4 和 BgNa(V)1.1）在非洲爪蟾卵母细胞中进行了药理学研究。BcsTx3 对果蝇 Shaker IR 通道具有高亲和力，超过 rKv1.2、hKv1.3 和 rKv1.6，对 NaV 通道没有活性。生化特性表明 BcsTx3 是一种由四个二硫键交联的 50 个氨基酸肽，序列比较表明 BcsTx3 属于一种新型作用于 K(V)通道的海葵毒素。此外，来自另外两种 Actiniaria 物种的与 BcsTx3 同源的假定毒素表明这种新发现的毒素家族具有古老的起源。
