ArticlePloS one2012
A chaperone trap contributes to the onset of cystic fibrosis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- General trends in the calnexin-dependent expression and pharmacological rescue of clinical CFTR variants.eLife · 2025Article
- General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants.bioRxiv : the preprint server for biology · 2025Article
- Unifying perspectives on the activity and genotypic targeting of pharmacological chaperones.The Journal of biological chemistry · 2025Review
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Proteostasis Landscapes of Cystic Fibrosis Variants Reveals Drug Response Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- Optimization of the fluorogen-activating protein tag for quantitative protein trafficking and colocalization studies inMolecular biology of the cell · 2024Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.Bioscience reports · 2022Review
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Distinct proteostasis states drive pharmacologic chaperone susceptibility for cystic fibrosis transmembrane conductance regulator misfolding mutants.Molecular biology of the cell · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- CyFi-MAP: an interactive pathway-based resource for cystic fibrosis.Scientific reports · 2021Article
- The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.Nature communications · 2021Article
- CFTR trafficking mutations disrupt cotranslational protein folding by targeting biosynthetic intermediates.Nature communications · 2020Article
- Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone.Cell chemical biology · 2020Article
- Selective Binding of HSC70 and its Co-Chaperones to Structural Hotspots on CFTR.Scientific reports · 2020Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a 'chaperone trap'. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF.
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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.