ArticleThe Journal of general physiology2015
Modulation of CFTR gating by permeant ions.
Article in The Journal of general physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 46 citations in OpenAlex.
- Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review.Current issues in molecular biology · 2025Review
- Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor.Molecules (Basel, Switzerland) · 2024Review
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein.eLife · 2023Article
- One Size Does Not Fit All: The Past, Present and Future of Cystic Fibrosis Causal Therapies.Cells · 2022Review
- Pharmacological Responses of the G542X-CFTR to CFTR Modulators.Frontiers in molecular biosciences · 2022Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Identification of binding sites for ivacaftor on the cystic fibrosis transmembrane conductance regulator.iScience · 2021Article
- Organoids as a personalized medicine tool for ultra-rare mutations in cystic fibrosis: The case of S955P and 1717-2A>G.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Positional effects of premature termination codons on the biochemical and biophysical properties of CFTR.The Journal of physiology · 2020Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- Article
- Structural mechanisms for defective CFTR gating caused by the Q1412X mutation, a severe Class VI pathogenic mutation in cystic fibrosis.The Journal of physiology · 2019Article
- Potentiation of the cystic fibrosis transmembrane conductance regulator by VX-770 involves stabilization of the pre-hydrolytic, OBritish journal of pharmacology · 2018Article
- Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.Biochimica et biophysica acta. Biomembranes · 2018Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- Functional characterization reveals that zebrafish CFTR prefers to occupy closed channel conformations.PloS one · 2018Article
- A common mechanism for CFTR potentiators.The Journal of general physiology · 2017Article
- Orkambi® and amplifier co-therapy improves function from a rareEMBO molecular medicine · 2017Article
- CFTR potentiators: from bench to bedside.Current opinion in pharmacology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is unique among ion channels in that after its phosphorylation by protein kinase A (PKA), its ATP-dependent gating violates microscopic reversibility caused by the intimate involvement of ATP hydrolysis in controlling channel closure. Recent studies suggest a gating model featuring an energetic coupling between opening and closing of the gate in CFTR's transmembrane domains and association and dissociation of its two nucleotide-binding domains (NBDs). We found that permeant ions such as nitrate can increase the open probability (Po) of wild-type (WT) CFTR by increasing the opening rate and decreasing the closing rate. Nearly identical effects were seen with a construct in which activity does not require phosphorylation of the regulatory domain, indicating that nitrate primarily affects ATP-dependent gating steps rather than PKA-dependent phosphorylation. Surprisingly, the effects of nitrate on CFTR gating are remarkably similar to those of VX-770 (N-(2,4-Di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide), a potent CFTR potentiator used in clinics. These include effects on single-channel kinetics of WT CFTR, deceleration of the nonhydrolytic closing rate, and potentiation of the Po of the disease-associated mutant G551D. In addition, both VX-770 and nitrate increased the activity of a CFTR construct lacking NBD2 (ΔNBD2), indicating that these gating effects are independent of NBD dimerization. Nonetheless, whereas VX-770 is equally effective when applied from either side of the membrane, nitrate potentiates gating mainly from the cytoplasmic side, implicating a common mechanism for gating modulation mediated through two separate sites of action.
Indexed as
Identifiers
What OpenQuestion holds
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.