2MI5

Structure of insect-specific sodium channel toxin mu-Dc1a

2MI5 の概要

• エントリーDOI: 10.2210/pdb2mi5/pdb
• NMR情報: BMRB: 19666
• 分子名称: Mu-diguetoxin-Dc1a (1 entity in total)
• 機能のキーワード: spider venom, insecticidal toxin, sodium channel, voltage-sensor, gating modifier, non-uniform sampling, dtx9.2, toxin, inhibitor cystine knot, knottin
• 由来する生物種: Diguetia canities (Desert bush spider)
• 細胞内の位置: Secreted: P49126
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6502.44

構造登録者

Bende, N.S.,Mobli, M.,King, G.F. (登録日: 2013-12-08, 公開日: 2014-07-23, 最終更新日: 2024-11-20)

主引用文献

Bende, N.S.,Dziemborowicz, S.,Mobli, M.,Herzig, V.,Gilchrist, J.,Wagner, J.,Nicholson, G.M.,King, G.F.,Bosmans, F.
A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a.
Nat Commun, 5:4350-4350, 2014

PubMed Abstract: 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.

PubMed: 25014760
DOI: 10.1038/ncomms5350

実験手法

SOLUTION NMR