Bende Niraj S, Dziemborowicz Sławomir, Mobli Mehdi, Herzig Volker, Gilchrist John, Wagner Jordan, Nicholson Graham M, King Glenn F, Bosmans Frank
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland QLD 4072, Australia.
School of Medical and Molecular Biosciences, University of Technology, Sydney, New South Wales 2007, Australia.
Nat Commun. 2014 Jul 11;5:4350. doi: 10.1038/ncomms5350.
β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1-S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.
β-地谷毒素-Dc1a（Dc1a）是一种来自沙漠灌木蜘蛛白纹遁蛛的毒素，它能在对哺乳动物无毒的浓度下使昆虫丧失活动能力。Dc1a能促进德国小蠊电压门控钠通道（BgNav1）开放，而人类钠通道对此不敏感。在此，通过将BgNav1电压感受器中常见的靶向S3b-S4桨状基序移植到Kv2.1中，我们发现Dc1a与结构域II电压感受器相互作用。相比之下，Dc1a对美国蟑螂的PaNav1通道介导的钠电流几乎没有影响，尽管它们的结构域II桨状基序相同。在探索导致PaNav1对Dc1a产生抗性的区域时，我们在BgNav1结构域II的S1-S2环内鉴定出两个残基，当它们突变为PaNav1对应的残基时，毒素敏感性会大幅降低。总体而言，我们的结果揭示了昆虫钠通道内一个独特的区域，该区域有助于确定对Dc1a的敏感性，这一概念对于设计昆虫选择性杀虫剂具有重要价值。
