ArticleJournal of molecular biology2008
Order-disorder-order transitions mediate the activation of cholera toxin.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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.
Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- ARF GTPases activate Salmonella effector SopF to ADP-ribosylate host V-ATPase and inhibit endomembrane damage-induced autophagy.Nature structural & molecular biology · 2022Article
- cAMP-Independent Activation of the Unfolded Protein Response by Cholera Toxin.Infection and immunity · 2021Article
- Tuning Allostery through Integration of Disorder to Order with a Residue Network.Biochemistry · 2020Article
- Quercetin-3-Rutinoside Blocks the Disassembly of Cholera Toxin by Protein Disulfide Isomerase.Toxins · 2019Article
- Review
- Protein disulfide isomerase does not act as an unfoldase in the disassembly of cholera toxin.Bioscience reports · 2018Article
- Cell Propagation of Cholera Toxin CTA ADP-Ribosylating Factor by Exosome Mediated Transfer.International journal of molecular sciences · 2018Article
- Carbohydrate inhibitors of cholera toxin.Beilstein journal of organic chemistry · 2018Review
- 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
- There is Diversity in Disorder-"In all Chaos there is a Cosmos, in all Disorder a Secret Order".Frontiers in molecular biosciences · 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
- Lipid rafts alter the stability and activity of the cholera toxin A1 subunit.The Journal of biological chemistry · 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
- Protein-disulfide isomerase displaces the cholera toxin A1 subunit from the holotoxin without unfolding the A1 subunit.The Journal of biological chemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cholera toxin (CT) holotoxin must be activated to intoxicate host cells. This process requires the intracellular dissociation of the enzymatic CTA1 domain from the holotoxin components CTA2 and B5, followed by subsequent interaction with the host factor ADP ribosylation factor 6 (ARF6)-GTP. We report the first NMR-based solution structural data for the CT enzymatic domain (CTA1). We show that this free enzymatic domain partially unfolds at the C-terminus and binds its protein partners at both the beginning and the end of this activation process. Deviations from random coil chemical shifts (Delta delta(coil)) indicate helix formation in the activation loop, which is essential to open the toxin's active site and occurs prior to its association with human protein ARF6. We performed NMR titrations of both free CTA1 and an active CTA1:ARF6-GTP complex with NAD(+), which revealed that the formation of the complex does not significantly enhance NAD(+) binding. Partial unfolding of CTA1 is further illustrated by using 4,4'-bis(1-anilinonaphthalene 8-sulfonate) fluorescence as an indicator of the exposed hydrophobic character of the free enzyme, which is substantially reduced when bound to ARF6-GTP. We propose that the primary role of ARF6's allostery is to induce refolding of the C-terminus of CTA1. Thus, as a folded globular toxin complex, CTA1 escapes the chaperone and proteasomal components of the endoplasmic reticulum associated degradation pathway in the cytosol and then proceeds to ADP ribosylate its target G(s)alpha, triggering the downstream events associated with the pathophysiology of cholera.
Indexed as
Identifiers
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.