ArticleeLife2017
Asymmetry of movements in CFTR's two ATP sites during pore opening serves their distinct functions.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Molecular and pharmacological evaluation of rare, cystic fibrosis-causing missense mutations of the CFTR channel.The Journal of physiology · 2025Article
- CRISPR/Cas9 bioluminescence-based assay for monitoring CFTR trafficking to the plasma membrane.Life science alliance · 2024Article
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Article
- Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein.eLife · 2023Article
- 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
- Directed Mutational Strategies Reveal Drug Binding and Transport by the MDR Transporters ofJournal of fungi (Basel, Switzerland) · 2021Review
- Strategies for cystic fibrosis transmembrane conductance regulator inhibition: from molecular mechanisms to treatment for secretory diarrhoeas.FEBS letters · 2020Review
- An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.Developmental cell · 2019Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- In vitro NTPase activity of highly purified Pdr5, a major yeast ABC multidrug transporter.Scientific reports · 2019Article
- Combining theoretical and experimental data to decipher CFTR 3D structures and functions.Cellular and molecular life sciences : CMLS · 2018Article
- Physiological and pharmacological characterization of the N1303K mutant CFTR.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2018Article
- Ribosome recycling is coordinated by processive events in two asymmetric ATP sites of ABCE1.Life science alliance · 2018Article
- Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
CFTR, the chloride channel mutated in cystic fibrosis (CF) patients, is opened by ATP binding to two cytosolic nucleotide binding domains (NBDs), but pore-domain mutations may also impair gating. ATP-bound NBDs dimerize occluding two nucleotides at interfacial binding sites; one site hydrolyzes ATP, the other is inactive. The pore opens upon tightening, and closes upon disengagement, of the catalytic site following ATP hydrolysis. Extent, timing, and role of non-catalytic-site movements are unknown. Here we exploit equilibrium gating of a hydrolysis-deficient mutant and apply Φ value analysis to compare timing of opening-associated movements at multiple locations, from the cytoplasmic ATP sites to the extracellular surface. Marked asynchrony of motion in the two ATP sites reveals their distinct roles in channel gating. The results clarify the molecular mechanisms of functional cross-talk between canonical and degenerate ATP sites in asymmetric ABC proteins, and of the gating defects caused by two common CF mutations.
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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.