ArticleJournal of molecular biology2009
Stabilization of the tertiary structure of the cholera toxin A1 subunit inhibits toxin dislocation and cellular intoxication.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- The cytopathic activity of cholera toxin requires a threshold quantity of cytosolic toxin.Cellular signalling · 2023Article
- Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins.Frontiers in cellular and infection microbiology · 2022Review
- cAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin.Infection and immunity · 2021Article
- A binding motif for Hsp90 in the A chains of ADP-ribosylating toxins that move from the endoplasmic reticulum to the cytosol.Cellular microbiology · 2019Article
- Stability and Conformational Resilience of Protein Disulfide Isomerase.Biochemistry · 2019Article
- Quercetin-3-Rutinoside Blocks the Disassembly of Cholera Toxin by Protein Disulfide Isomerase.Toxins · 2019Article
- Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process.International journal of molecular sciences · 2019Review
- Protein disulfide isomerase does not act as an unfoldase in the disassembly of cholera toxin.Bioscience reports · 2018Article
- Thermal Unfolding of the Pertussis Toxin S1 Subunit Facilitates Toxin Translocation to the Cytosol by the Mechanism of Endoplasmic Reticulum-Associated Degradation.Infection and immunity · 2016Article
- A Conformational Shift in the Dissociated Cholera Toxin A1 Subunit Prevents Reassembly of the Cholera Holotoxin.Toxins · 2015Article
- Co- and post-translocation roles for HSP90 in cholera Intoxication.The Journal of biological chemistry · 2014Article
- ADP-ribosylation factor 6 acts as an allosteric activator for the folded but not disordered cholera toxin A1 polypeptide.Molecular microbiology · 2014Article
- Substrate-induced unfolding of protein disulfide isomerase displaces the cholera toxin A1 subunit from its holotoxin.PLoS pathogens · 2014Article
- Toxin instability and its role in toxin translocation from the endoplasmic reticulum to the cytosol.Biomolecules · 2013Article
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- Lipid rafts alter the stability and activity of the cholera toxin A1 subunit.The Journal of biological chemistry · 2012Article
- Detection of toxin translocation into the host cytosol by surface plasmon resonance.Journal of visualized experiments : JoVE · 2012Article
- Insights on the trafficking and retro-translocation of glycosphingolipid-binding bacterial toxins.Frontiers in cellular and infection microbiology · 2012Review
- Structural and functional interactions between the cholera toxin A1 subunit and ERdj3/HEDJ, a chaperone of the endoplasmic reticulum.Infection and immunity · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER) by retrograde vesicular transport. The catalytic subunit of CT (CTA1) then crosses the ER membrane and enters the cytosol in a process that involves the quality control mechanism of ER-associated degradation. The molecular details of this dislocation event have not been fully characterized. Here, we report that thermal instability in the CTA1 subunit-specifically, the loss of CTA1 tertiary structure at 37 degrees C-triggers toxin dislocation. Biophysical studies found that glycerol preferentially stabilized the tertiary structure of CTA1 without having any noticeable effect on the thermal stability of its secondary structure. The thermal disordering of CTA1 tertiary structure normally preceded the perturbation of its secondary structure, but in the presence of 10% glycerol the temperature-induced loss of CTA1 tertiary structure occurred at higher temperatures in tandem with the loss of CTA1 secondary structure. The glycerol-induced stabilization of CTA1 tertiary structure blocked CTA1 dislocation from the ER and instead promoted CTA1 secretion into the extracellular medium. This, in turn, inhibited CT intoxication. Glycerol treatment also inhibited the in vitro degradation of CTA1 by the core 20S proteasome. Collectively, these findings indicate that toxin thermal instability plays a key role in the intoxication process. They also suggest the stabilization of CTA1 tertiary structure is a potential goal for novel antitoxin therapeutic agents.
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