ReviewToxicon : official journal of the International Society on Toxinology2009
Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel.
Review in Toxicon : official journal of the International Society on Toxinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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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.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Combined treatment with antitoxin and 3,4-diaminopyridine improves survival outcomes after lethal botulinum neurotoxin challenge.Molecular medicine (Cambridge, Mass.) · 2025Article
- Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.The Journal of pharmacology and experimental therapeutics · 2024Article
- A DARPin promotes faster onset of botulinum neurotoxin A1 action.Nature communications · 2023Article
- Crystal Structure of the Catalytic Domain of a Botulinum Neurotoxin Homologue fromInternational journal of molecular sciences · 2023Article
- A Comprehensive Structural Analysis ofToxins · 2023Review
- Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications.Toxins · 2022Review
- In Silico Conformational Features of Botulinum Toxins A1 and E1 According to Intraluminal Acidification.Toxins · 2022Article
- Antidotal treatment of botulism in rats by continuous infusion with 3,4-diaminopyridine.Molecular medicine (Cambridge, Mass.) · 2022Article
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- Article
- Structural flexibility of the tetanus neurotoxin revealed by crystallographic and solution scattering analyses.Journal of structural biology: X · 2021Article
- Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins.Cell reports · 2020Article
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- A viral-fusion-peptide-like molecular switch drives membrane insertion of botulinum neurotoxin A1.Nature communications · 2018Article
- Use-dependent potentiation of voltage-gated calcium channels rescues neurotransmission in nerve terminals intoxicated by botulinum neurotoxin serotype A.Scientific reports · 2017Article
- Article
- Structural and functional analysis of botulinum neurotoxin subunits for pH-dependent membrane channel formation and translocation.Biochimica et biophysica acta · 2015Article
- The C-terminal heavy-chain domain of botulinum neurotoxin a is not the only site that binds neurons, as the N-terminal heavy-chain domain also plays a very active role in toxin-cell binding and interactions.Infection and immunity · 2015Article
- The blockade of the neurotransmitter release apparatus by botulinum neurotoxins.Cellular and molecular life sciences : CMLS · 2014Review
- Cargo-delivery platforms for targeted delivery of inhibitor cargos against botulism.Current topics in medicinal chemistry · 2014Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Clostridial botulinum neurotoxins (BoNTs) inhibit synaptic exocytosis; intoxication requires the di-chain protein to undergo conformational changes in response to pH and redox gradients across the endosomal membrane with consequent formation of a protein-conducting channel by the heavy chain (HC) that translocates the light chain (LC) protease into the cytosol, colocalizing it with the substrate SNARE proteins. We investigate the dynamics of protein translocation across membranes using a sensitive single-molecule assay to track translocation events with millisecond resolution on lipid bilayers and on membrane patches of Neuro 2A cells. Translocation of BoNT/A LC by the HC is observed in real time as changes of channel conductance: the channel is occluded by the light chain during transit, and open after completion of translocation and release of cargo, acting intriguingly similar to the protein-conducting/translocating channels of the endoplasmic reticulum, mitochondria, and chloroplasts. Our findings support the notion of an interdependent, tight interplay between the HC transmembrane chaperone and the LC cargo that prevents LC aggregation and dictates the productive passage of cargo through the channel and completion of translocation. The protein-conducting channel of BoNT, a key element in the process of neurotoxicity, emerges therefore as a target for antidote discovery - a novel paradigm of paramount significance to health science and biodefense.
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What OpenQuestion holds
Registered trials
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.