Departamento de Física e Química da Faculdade de Ciências Farmacêuticas de Ribeirão Preto da Universidade de São Paulo-FCFRP-USP, Av. do Café, s/n, 14040-903 Ribeirão Preto-SP, Brazil.
Toxicon. 2011 Jul;58(1):54-61. doi: 10.1016/j.toxicon.2011.05.001. Epub 2011 May 13.
Voltage-gated potassium channel toxins (KTxs) are basic short chain peptides comprising 23-43 amino acid residues that can be cross-linked by 3 or 4 disulfide bridges. KTxs are classified into four large families: α-, β-, γ- and κ-KTx. These peptides display varying selectivity and affinity for K(v) channel subtypes. In this work, a novel toxin from the Tityus serrulatus venom was isolated, characterized and submitted to a wide electrophysiological screening on 5 different subtypes of Na(V) channels (Na(V)1.4; Na(V)1.5; Na(V)1.6; Na(V)1.8 and DmNa(V)1) and 12 different subtypes of K(V) 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; Shaker IR and ERG). This novel peptide, named Ts15, has 36 amino acids, is cross-linked by 3 disulfide bridges, has a molecular mass of 3956 Da and pI around 9. Electrophysiological experiments using patch clamp and the two-electrode voltage clamp techniques show that Ts15 preferentially blocks K(V)1.2 and K(V)1.3 channels with an IC₅₀ value of 196 ± 25 and 508 ± 67 nM, respectively. No effect on Na(V) channels was observed, at all tested concentrations. Since Ts15 shows low amino acid identity with other known KTxs, it was considered a bona fide novel type of scorpion toxin. Ts15 is the unique member of the new α-Ktx21 subfamily and therefore was classified as α-Ktx21.1.
电压门控钾通道毒素（KTxs）是由 23-43 个氨基酸残基组成的碱性短链肽，可通过 3 或 4 个二硫键交联。KTxs 分为四个大家族：α-、β-、γ-和 κ-KTx。这些肽显示出对 K(v)通道亚型的不同选择性和亲和力。在这项工作中，从 Tityus serrulatus 毒液中分离出一种新型毒素，对 5 种不同亚型的 Na(V)通道（Na(V)1.4；Na(V)1.5；Na(V)1.6；Na(V)1.8 和 DmNa(V)1）和 12 种不同亚型的 K(V)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；Shaker IR 和 ERG）进行了广泛的电生理筛选。这种新型肽，命名为 Ts15，由 36 个氨基酸组成，通过 3 个二硫键交联，分子量为 3956 Da，pI 约为 9。使用膜片钳和双电极电压钳技术进行的电生理实验表明，Ts15 优先阻断 K(V)1.2 和 K(V)1.3 通道，IC₅₀ 值分别为 196 ± 25 和 508 ± 67 nM。在所有测试浓度下，对 Na(V)通道均无影响。由于 Ts15 与其他已知 KTxs 的氨基酸同源性较低，因此被认为是一种新型的蝎毒素。Ts15 是新的 α-Ktx21 亚家族的唯一成员，因此被归类为 α-Ktx21.1。
