ArticleNature communications2017
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Triple potentiator combinations increase the functional correction of several CFTR gating mutants.npj drug discovery · 2026Article
- FKBP8 connects the Hsp70-Hsp90 chaperone machinery to the folding of membrane proteins.Nature communications · 2026Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- Comparing ATPase activity of ATP-binding cassette subfamily C member 4, lamprey CFTR, and human CFTR using an antimony-phosphomolybdate assay.Frontiers in pharmacology · 2024Article
- Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations.Frontiers in pharmacology · 2024Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Function Investigations and Applications of Membrane Proteins on Artificial Lipid Membranes.International journal of molecular sciences · 2023Review
- The COPD-Associated Polymorphism Impairs the CFTR Function to Suppress Excessive IL-8 Production upon Environmental Pathogen Exposure.International journal of molecular sciences · 2023Article
- Redefining Hypo- and Hyper-Responding Phenotypes of CFTR Mutants for Understanding and Therapy.International journal of molecular sciences · 2022Article
- Triangulating variation in the population to define mechanisms for precision management of genetic disease.Structure (London, England : 1993) · 2022Article
- Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.Journal of medicinal chemistry · 2022Review
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- Ubr1-induced selective endophagy/autophagy protects against the endosomal and CaCellular and molecular life sciences : CMLS · 2022Article
- Proximity Profiling of the CFTR Interaction Landscape in Response to Orkambi.International journal of molecular sciences · 2022Article
- Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?International journal of molecular sciences · 2022Review
- Volleying plasma membrane proteins from birth to death: Role of J-domain proteins.Frontiers in molecular biosciences · 2022Review
- Probing Allosteric Hsp70 Inhibitors by Molecular Modelling Studies to Expedite the Development of Novel Combined F508del CFTR Modulators.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021Review
- Membrane proteins enter the fold.Current opinion in structural biology · 2021Review
- Lumacaftor and Matrine: Possible Therapeutic Combination to Counteract the Inflammatory Process in Cystic Fibrosis.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (∆F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 °C and concomitant functional inactivation of ∆F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at single-molecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of ∆F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases.The F508 deletion (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. Here the authors show that cytosolic chaperones shift the F508del channel conformation to the native fold by kinetic and thermodynamic remodelling of the gating energetics towards that of wild-type CTFR.
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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.