ArticleThe Journal of biological chemistry2019
HSC70 and HSP90 chaperones perform complementary roles in translocation of the cholera toxin A1 subunit from the endoplasmic reticulum to the cytosol.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 21 citations in OpenAlex.
- Salmonella enterica serovar typhi limits the potency of typhoid toxin and ADP-ribosylating toxin AB to establish a persistent infection.FEBS open bio · 2026Article
- The antiarrhythmic drugs amiodarone and dronedarone inhibit intoxication of cells with pertussis toxin.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?Lipids in health and disease · 2024Article
- The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.Toxins · 2024Article
- Reduction is sufficient for the disassembly of ricin and Shiga toxin 1 but notInfection and immunity · 2023Article
- Domperidone Protects Cells from Intoxication withToxins · 2023Article
- [HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins.Frontiers in cellular and infection microbiology · 2022Review
- A new role of GRP75-USP1-SIX1 protein complex in driving prostate cancer progression and castration resistance.Oncogene · 2021Article
- Intoxication of mammalian cells with binary clostridial enterotoxins is inhibited by the combination of pharmacological chaperone inhibitors.Naunyn-Schmiedeberg's archives of pharmacology · 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
- Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.Scientific reports · 2021Article
- Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.Frontiers in cellular and infection microbiology · 2021Article
- Crystal Structure of Exotoxin A fromToxins · 2020Article
- Review
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5 authors at 1 institution in 1 country.
Funding
Abstract
Cholera toxin (CT) travels by vesicle carriers from the cell surface to the endoplasmic reticulum (ER) where the catalytic A1 subunit of CT (CTA1) dissociates from the rest of the toxin, unfolds, and moves through a membrane-spanning translocon pore to reach the cytosol. Heat shock protein 90 (HSP90) binds to the N-terminal region of CTA1 and facilitates its ER-to-cytosol export by refolding the toxin as it emerges at the cytosolic face of the ER membrane. HSP90 also refolds some endogenous cytosolic proteins as part of a foldosome complex containing heat shock cognate 71-kDa protein (HSC70) and the HSC70/HSP90-organizing protein (HOP) linker that anchors HSP90 to HSC70. We accordingly predicted that HSC70 and HOP also function in CTA1 translocation. Inactivation of HSC70 by drug treatment disrupted CTA1 translocation to the cytosol and generated a toxin-resistant phenotype. In contrast, the depletion of HOP did not disrupt CT activity against cultured cells. HSC70 and HSP90 could bind independently to disordered CTA1, even in the absence of HOP. This indicated HSP90 and HSC70 recognize distinct regions of CTA1, which was confirmed by the identification of a YYIYVI-binding motif for HSC70 that spans residues 83-88 of the 192-amino acid CTA1 polypeptide. Refolding of disordered CTA1 occurred in the presence of HSC70 alone, indicating that HSC70 and HSP90 can each independently refold CTA1. Our work suggests a novel translocation mechanism in which sequential interactions with HSP90 and HSC70 drive the N- to C-terminal extraction of CTA1 from the ER.
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