ArticleThe Journal of biological chemistry2014
Calcium, acylation, and molecular confinement favor folding of Bordetella pertussis adenylate cyclase CyaA toxin into a monomeric and cytotoxic form.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Pasteurian Contributions to the Study ofToxins · 2023Pooled it
- Covalently Linked Peptides and Membrane Potential Enable CyaA Segment Translocation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Membrane Interaction Characteristics of the RTX Toxins and the Cholesterol-Dependence of Their Cytolytic/Cytotoxic Activity.International journal of molecular sciences · 2024Review
- CyaA translocation across eukaryotic cell membranes.Frontiers in molecular biosciences · 2024Article
- B2LiVe, a label-free 1D-NMR method to quantify the binding of amphitropic peptides or proteins to membrane vesicles.Cell reports methods · 2023Article
- Heterologously secreted MbxA from Moraxella bovis induces a membrane blebbing response of the human host cell.Scientific reports · 2022Article
- A Robust and Sensitive Spectrophotometric Assay for the Enzymatic Activity of Bacterial Adenylate Cyclase Toxins.Toxins · 2022Article
- Article
- Dynamics and structural changes of calmodulin upon interaction with the antagonist calmidazolium.BMC biology · 2022Article
- Review
- Cholesterol stimulates the lytic activity of Adenylate Cyclase Toxin on lipid membranes by promoting toxin oligomerization and formation of pores with a greater effective size.The FEBS journal · 2021Article
- Different roles of conserved tyrosine residues of the acylated domains in folding and activity of RTX toxins.Scientific reports · 2021Article
- A High-Affinity Calmodulin-Binding Site in the CyaA Toxin Translocation Domain is Essential for Invasion of Eukaryotic Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Retargeting from the CR3 to the LFA-1 receptor uncovers the adenylyl cyclase enzyme-translocating segment ofThe Journal of biological chemistry · 2020Article
- Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins.The Journal of biological chemistry · 2020Article
- Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin.PloS one · 2020Article
- Membrane Permeabilization byBiomolecules · 2019Article
- The Adenylate Cyclase (CyaA) Toxin fromToxins · 2019Article
- Article
- Cytotoxic activity of Kingella kingae RtxA toxin depends on post-translational acylation of lysine residues and cholesterol binding.Emerging microbes & infections · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenylate cyclase (CyaA) toxin, a multidomain protein of 1706 amino acids, is one of the major virulence factors produced by Bordetella pertussis, the causative agent of whooping cough. CyaA is able to invade eukaryotic target cells in which it produces high levels of cAMP, thus altering the cellular physiology. Although CyaA has been extensively studied by various cellular and molecular approaches, the structural and functional states of the toxin remain poorly characterized. Indeed, CyaA is a large protein and exhibits a pronounced hydrophobic character, making it prone to aggregation into multimeric forms. As a result, CyaA has usually been extracted and stored in denaturing conditions. Here, we define the experimental conditions allowing CyaA folding into a monomeric and functional species. We found that CyaA forms mainly multimers when refolded by dialysis, dilution, or buffer exchange. However, a significant fraction of monomeric, folded protein could be obtained by exploiting molecular confinement on size exclusion chromatography. Folding of CyaA into a monomeric form was found to be critically dependent upon the presence of calcium and post-translational acylation of the protein. We further show that the monomeric preparation displayed hemolytic and cytotoxic activities suggesting that the monomer is the genuine, physiologically active form of the toxin. We hypothesize that the structural role of the post-translational acylation in CyaA folding may apply to other RTX toxins.
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