Evidence map›Paper›PMID 23473802›Full record

ArticleBiochemical pharmacology2013

The insecticidal neurotoxin Aps III is an atypical knottin peptide that potently blocks insect voltage-gated sodium channels.

Niraj S Bende, Eunji Kang, Volker Herzig, Frank Bosmans, Graham M Nicholson, Mehdi Mobli, Glenn F King

Open access · greenAbstract read
In one paragraph

Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  7. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Isolation of two insecticidal toxins from venom of the Australian theraphosid spider Coremiocnemis tropix.Toxicon : official journal of the International Society on Toxinology · 2016
    Article
  14. Article
  15. Article
  16. Molecular biology of insect sodium channels and pyrethroid resistance.Insect biochemistry and molecular biology · 2014
    Article
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Niraj S BendeInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
Eunji Kang
Volker Herzig
Frank Bosmans
Graham M Nicholson
Mehdi Mobli
Glenn F King
University of Queensland · AUUniversity of Technology Sydney · AUJohns Hopkins University · US

Funding

The influence of beta-subunits and sphingomyelin on sodium channel functionR00NS073797 · NINDS · JOHNS HOPKINS UNIVERSITY · PI BOSMANS, FRANK GERT WERNER · 2012 to 2014
$730k
NINDS NIH HHS R00 NS073797NINDS NIH HHS R00NS073797
6 · The paper itself

Abstract

One of the most potent insecticidal venom peptides described to date is Aps III from the venom of the trapdoor spider Apomastus schlingeri. Aps III is highly neurotoxic to lepidopteran crop pests, making it a promising candidate for bioinsecticide development. However, its disulfide-connectivity, three-dimensional structure, and mode of action have not been determined. Here we show that recombinant Aps III (rAps III) is an atypical knottin peptide; three of the disulfide bridges form a classical inhibitor cystine knot motif while the fourth disulfide acts as a molecular staple that restricts the flexibility of an unusually large β hairpin loop that often houses the pharmacophore in this class of toxins. We demonstrate that the irreversible paralysis induced in insects by rAps III results from a potent block of insect voltage-gated sodium channels. Channel block by rAps III is voltage-independent insofar as it occurs without significant alteration in the voltage-dependence of channel activation or steady-state inactivation. Thus, rAps III appears to be a pore blocker that plugs the outer vestibule of insect voltage-gated sodium channels. This mechanism of action contrasts strikingly with virtually all other sodium channel modulators isolated from spider venoms that act as gating modifiers by interacting with one or more of the four voltage-sensing domains of the channel.

Indexed as

Amino Acid SequenceAnimalsCystine-Knot MiniproteinsDipteraDisulfidesEscherichia coliInsect ProteinsKineticsMembrane PotentialsModels, MolecularMolecular Sequence DataNeuronsNeurotoxinsPatch-Clamp TechniquesPeriplanetaPrimary Cell CultureCystine-Knot MiniproteinsDisulfidesInsect ProteinsNeurotoxinsRecombinant ProteinsSodium Channel BlockersSpider VenomsVoltage-Gated Sodium Channels

Identifiers

PMID23473802
PMCPMC3654253
OpenAlexW2007597690

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.