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首页> 外文期刊>Biochemical Pharmacology >Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): The first member of a new κ-KTX subfamily
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Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): The first member of a new κ-KTX subfamily

机译：HelaTx1（Heterometrus laoticus）的纯化，分子克隆和功能表征：一个新的κ-KTX亚家族的第一个成员

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Given their medical importance, most attention has been paid toward the venom composition of scorpions of the Buthidae family. Nevertheless, research has shown that the venom of scorpions of other families is also a remarkable source of unique peptidyl toxins. The κ-KTx family of voltage-gated potassium channel (VGPC) scorpion toxins is hereof an example. From the telson of the scorpion Heterometrus laoticus (Scorpionidae), a peptide, HelaTx1, with unique primary sequence was purified through HPLC and sequenced by Edman degradation. Based on the amino acid sequence, the peptide could be cloned and the cDNA sequence revealed. HelaTx1 was chemically synthesized and functionally characterized on VGPCs of the Shaker-related, Shab-related, Shaw-related and Shal-related subfamilies. Furthermore, the toxin was also tested on small- and intermediate conductance Ca 2+-activated K + channels. From the channels studied, K v1.1 and K v1.6 were found to be the most sensitive (K v1.1 EC 50 = 9.9 ± 1.6 μM). The toxin did not alter the activation of the channels. Competition experiments with TEA showed that the toxin is a pore blocker. Mutational studies showed that the residues E353 and Y379 in the pore of K v1.1 act as major interaction points for binding of the toxin. Given the amino acid sequence, the predicted secondary structure and the biological activity on VGPCs, HelaTx1 should be included in the κ-KTX family. Based on a phylogenetic study, we rearranged this family of VGPC toxins into five subfamilies and suggest that HelaTx1 is the first member of the new κ-KTx5 subfamily.
机译：考虑到它们的医学重要性，大多数注意力都集中在了Buthidae家族蝎子的毒液成分上。尽管如此，研究表明，其他家族的蝎子的毒液也是独特的肽基毒素的重要来源。电压门控钾通道（VGPC）蝎毒素的κ-KTx家族是一个例子。从蝎蝎异蝇（Scorpionidae）的telson中，通过HPLC纯化具有唯一一级序列的肽HelaTx1，并通过Edman降解进行测序。根据氨基酸序列，可以克隆该肽并揭示cDNA序列。 HelaTx1是化学合成的，并在与Shaker相关，Shab相关，Shaw相关和Shal相关的亚家族的VGPC上进行了功能表征。此外，还对中小型电导Ca 2+激活的K +通道进行了毒素测试。从研究的通道中，发现K v1.1和K v1.6是最敏感的（K v1.1 EC 50 = 9.9±1.6μM）。毒素没有改变通道的激活。与TEA的竞争实验表明，该毒素是一种毛孔阻断剂。突变研究表明，K v1.1孔中的残基E353和Y379是毒素结合的主要相互作用点。给定氨基酸序列，预测的二级结构和对VGPC的生物学活性，HelaTx1应该包括在κ-KT​​X家族中。根据系统发育研究，我们将该VGPC毒素家族重新排列为五个亚家族，并建议HelaTx1是新的κ-KTx5亚家族的第一个成员。

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