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A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

Author
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Abstract
beta-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 (Na-v) channels (BgNa(v)1), whereas human Na-v channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNa(v)1 voltage sensors into K(v)2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNa(v)1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNa(v)1 resistance to Dc1a, we identified two residues within the BgNa(v)1 domain II S1-S2 loop that when mutated to their PaNa(v)1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Na-v channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.
Keywords
SHAKER K+ CHANNEL, BETA-SCORPION TOXIN, TARANTULA TOXINS, PEPTIDE TOXINS, VENOM PEPTIDES, POTASSIUM CHANNELS, DIGUETIA CANITIES, CRYSTAL-STRUCTURE, GATING CHARGE, RECEPTOR-SITE

Citation

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MLA
Bende, Niraj S, Slawomir Dziemborowicz, Mehdi Mobli, et al. “A Distinct Sodium Channel Voltage-sensor Locus Determines Insect Selectivity of the Spider Toxin Dc1a.” NATURE COMMUNICATIONS 5 (2014): n. pag. Print.
APA
Bende, N. S., Dziemborowicz, S., Mobli, M., Herzig, V., Gilchrist, J., Wagner, J., Nicholson, G. M., et al. (2014). A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. NATURE COMMUNICATIONS, 5.
Chicago author-date
Bende, Niraj S, Slawomir Dziemborowicz, Mehdi Mobli, Volker Herzig, John Gilchrist, Jordan Wagner, Graham M Nicholson, Glenn F King, and Frank Bosmans. 2014. “A Distinct Sodium Channel Voltage-sensor Locus Determines Insect Selectivity of the Spider Toxin Dc1a.” Nature Communications 5.
Chicago author-date (all authors)
Bende, Niraj S, Slawomir Dziemborowicz, Mehdi Mobli, Volker Herzig, John Gilchrist, Jordan Wagner, Graham M Nicholson, Glenn F King, and Frank Bosmans. 2014. “A Distinct Sodium Channel Voltage-sensor Locus Determines Insect Selectivity of the Spider Toxin Dc1a.” Nature Communications 5.
Vancouver
1.
Bende NS, Dziemborowicz S, Mobli M, Herzig V, Gilchrist J, Wagner J, et al. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a. NATURE COMMUNICATIONS. 2014;5.
IEEE
[1]
N. S. Bende et al., “A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a,” NATURE COMMUNICATIONS, vol. 5, 2014.
@article{8584522,
  abstract     = {{beta-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 (Na-v) channels (BgNa(v)1), whereas human Na-v channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNa(v)1 voltage sensors into K(v)2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNa(v)1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNa(v)1 resistance to Dc1a, we identified two residues within the BgNa(v)1 domain II S1-S2 loop that when mutated to their PaNa(v)1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Na-v channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.}},
  articleno    = {{4350}},
  author       = {{Bende, Niraj S and Dziemborowicz, Slawomir and Mobli, Mehdi and Herzig, Volker and Gilchrist, John and Wagner, Jordan and Nicholson, Graham M and King, Glenn F and Bosmans, Frank}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{SHAKER K+ CHANNEL,BETA-SCORPION TOXIN,TARANTULA TOXINS,PEPTIDE TOXINS,VENOM PEPTIDES,POTASSIUM CHANNELS,DIGUETIA CANITIES,CRYSTAL-STRUCTURE,GATING CHARGE,RECEPTOR-SITE}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a}},
  url          = {{http://dx.doi.org/10.1038/ncomms5350}},
  volume       = {{5}},
  year         = {{2014}},
}

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