ArticleCells2019
Cholesterol Interaction Directly Enhances Intrinsic Activity of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed.
- Article
- Review
- High-throughput functional assay in cystic fibrosis patient-derived organoids allows drug repurposing.ERJ open research · 2023Article
- Elexacaftor/Tezacaftor/Ivacaftor Accelerates Wound Repair in Cystic Fibrosis Airway Epithelium.Journal of personalized medicine · 2022Article
- A protocol for identifying the binding sites of small molecules on the cystic fibrosis transmembrane conductance regulator (CFTR) protein.STAR protocols · 2022Article
- Identification of binding sites for ivacaftor on the cystic fibrosis transmembrane conductance regulator.iScience · 2021Article
- Rescue of multiple class II CFTR mutations by elexacaftor+tezacaftor+ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator.The European respiratory journal · 2021Article
- Phenotyping Rare CFTR Mutations Reveal Functional Expression Defects Restored by TRIKAFTAJournal of personalized medicine · 2021Article
- Is the ENaC Dysregulation in CF an Effect of Protein-Lipid Interaction in the Membranes?International journal of molecular sciences · 2021Review
- Alteration of Membrane Cholesterol Content Plays a Key Role in Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Channel Activity.Frontiers in physiology · 2021Article
- Preclinical Studies of a Rare CF-Causing Mutation in the Second Nucleotide Binding Domain (c.3700A>G) Show Robust Functional Rescue in Primary Nasal Cultures by Novel CFTR Modulators.Journal of personalized medicine · 2020Article
- Structural basis of trehalose recycling by the ABC transporter LpqY-SugABC.Science advances · 2020Article
- Distinctive lipid signatures of bronchial epithelial cells associated with cystic fibrosis drugs, including Trikafta.JCI insight · 2020Article
- Proteomics and Metabolomics for Cystic Fibrosis Research.International journal of molecular sciences · 2020Review
- Allele-Specific Prevention of Nonsense-Mediated Decay in Cystic Fibrosis Using Homology-Independent Genome Editing.Molecular therapy. Methods & clinical development · 2020Article
- The CFTR Mutation c.3453G > C (D1152H) Confers an Anion Selectivity Defect in Primary Airway Tissue that Can Be Rescued by Ivacaftor.Journal of personalized medicine · 2020Article
- Activity of lumacaftor is not conserved in zebrafish Cftr bearing the major cystic fibrosis-causing mutation.FASEB bioAdvances · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The recent cryo-electron microscopy structures of zebrafish and the human cystic fibrosis transmembrane conductance regulator (CFTR) provided unprecedented insights into putative mechanisms underlying gating of its anion channel activity. Interestingly, despite predictions based on channel activity measurements in biological membranes, the structure of the detergent purified, phosphorylated, and ATP-bound human CFTR protein did not reveal a stably open conduction pathway. This study tested the hypothesis that the functional properties of the detergent solubilized CFTR protein used for structural determinations are different from those exhibited by CFTR purified under conditions that retain associated lipids native to the membrane. It was found that CFTR purified together with phospholipids and cholesterol using amphipol: A8-35, exhibited higher rates of catalytic activity, phosphorylation dependent channel activation and potentiation by the therapeutic compound, ivacaftor, than did CFTR purified in detergent. The catalytic activity of phosphorylated CFTR detergent micelles was rescued by the addition of phospholipids plus cholesterol, but not by phospholipids alone, arguing for a specific role for cholesterol in modulating this function. In summary, these studies highlight the importance of lipid interactions in the intrinsic activities and pharmacological potentiation of CFTR.
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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.