ArticleProceedings of the National Academy of Sciences of the United States of America2010
Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83 citing papers in PubMed, 118 citations in OpenAlex.
- Altered functional interactions between CFTR disease mutants ΔF508 and G551D and the protein kinase A catalytic subunit.The Journal of physiology · 2026Article
- Molecular and pharmacological evaluation of rare, cystic fibrosis-causing missense mutations of the CFTR channel.The Journal of physiology · 2025Article
- Structure of CFTR bound to (R)-BPO-27 unveils a pore-blockage mechanism.Nature communications · 2025Article
- A fluorescent probe for the enzymatic activity of KbioRxiv : the preprint server for biology · 2025Article
- Structural determinants of protein kinase A essential for CFTR channel activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution.Nature structural & molecular biology · 2024Article
- Structural basis for CFTR inhibition by CFTRProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural identification of a selectivity filter in CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 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
- Optimization of CFTR gating through the evolution of its extracellular loops.The Journal of general physiology · 2023Article
- Article
- A review of the pathophysiology and the role of ion channels on bronchial asthma.Frontiers in pharmacology · 2023Review
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond.eLife · 2021Article
- Functional stability of CFTR depends on tight binding of ATP at its degenerate ATP-binding site.The Journal of physiology · 2021Article
- Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.Life (Basel, Switzerland) · 2021Review
- Role of Protein Kinase A-Mediated Phosphorylation in CFTR Channel Activity Regulation.Frontiers in physiology · 2021Review
- Strategies for cystic fibrosis transmembrane conductance regulator inhibition: from molecular mechanisms to treatment for secretory diarrhoeas.FEBS letters · 2020Review
- Characterization of the kinetic cycle of an ABC transporter by single-molecule and cryo-EM analyses.eLife · 2020Article
23 more citing papers are in PubMed but not listed here.
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3 authors at 3 institutions in 3 countries.
Funding
Abstract
CFTR, the ABC protein defective in cystic fibrosis, functions as an anion channel. Once phosphorylated by protein kinase A, a CFTR channel is opened and closed by events at its two cytosolic nucleotide binding domains (NBDs). Formation of a head-to-tail NBD1/NBD2 heterodimer, by ATP binding in two interfacial composite sites between conserved Walker A and B motifs of one NBD and the ABC-specific signature sequence of the other, has been proposed to trigger channel opening. ATP hydrolysis at the only catalytically competent interfacial site is suggested to then destabilize the NBD dimer and prompt channel closure. But this gating mechanism, and how tightly CFTR channel opening and closing are coupled to its catalytic cycle, remains controversial. Here we determine the distributions of open burst durations of individual CFTR channels, and use maximum likelihood to evaluate fits to equilibrium and nonequilibrium mechanisms and estimate the rate constants that govern channel closure. We examine partially and fully phosphorylated wild-type CFTR channels, and two mutant CFTR channels, each bearing a deleterious mutation in one or other composite ATP binding site. We show that the wild-type CFTR channel gating cycle is essentially irreversible and tightly coupled to the ATPase cycle, and that this coupling is completely destroyed by the NBD2 Walker B mutation D1370N but only partially disrupted by the NBD1 Walker A mutation K464A.
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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.