ArticleThe Journal of physiology2006
The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 62 citations in OpenAlex.
- Esc peptides and derivatives potentiate the activity of CFTR with gating defects and display antipseudomonal activity in cystic fibrosis-like lung disease.Cellular and molecular life sciences : CMLS · 2025Article
- Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1.Computational and structural biotechnology journal · 2022Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- A topological switch in CFTR modulates channel activity and sensitivity to unfolding.Nature chemical biology · 2021Article
- VX-770-mediated potentiation of numerous human CFTR disease mutants is influenced by phosphorylation level.Scientific reports · 2019Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.Biochimica et biophysica acta. Biomembranes · 2018Article
- Molecular dynamics simulation study on the structural instability of the most common cystic fibrosis-associated mutant ΔF508-CFTR.Biophysics and physicobiology · 2018Article
- A common mechanism for CFTR potentiators.The Journal of general physiology · 2017Article
- Deletion of Phenylalanine 508 in the First Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator Increases Conformational Exchange and Inhibits Dimerization.The Journal of biological chemistry · 2015Article
- A stable human-cell system overexpressing cystic fibrosis transmembrane conductance regulator recombinant protein at the cell surface.Molecular biotechnology · 2015Article
- Full-open and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics.Cellular and molecular life sciences : CMLS · 2015Article
- Cysteine accessibility probes timing and extent of NBD separation along the dimer interface in gating CFTR channels.The Journal of general physiology · 2015Article
- Rational Coupled Dynamics Network Manipulation Rescues Disease-Relevant Mutant Cystic Fibrosis Transmembrane Conductance Regulator.Chemical science · 2015Article
- Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.Science translational medicine · 2014Article
- The silent codon change I507-ATC->ATT contributes to the severity of the ΔF508 CFTR channel dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Allosteric coupling between the intracellular coupling helix 4 and regulatory sites of the first nucleotide-binding domain of CFTR.PloS one · 2013Article
- Article
- Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR.Journal of molecular biology · 2012Article
- Role of the juxtamembrane region of cytoplasmic loop 3 in the gating and conductance of the cystic fibrosis transmembrane conductance regulator chloride channel.Biochemistry · 2012Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel employing the ABC transporter structural motif. Deletion of a single residue (Phe508) in the first nucleotide-binding domain (NBD1), which occurs in most patients with cystic fibrosis, impairs both maturation and function of the protein. However, substitution of the Phe508 with small uncharged amino acids, including cysteine, is permissive for maturation. To explore the possible role of the phenylalanine aromatic side chain in channel gating we introduced a cysteine at this position in cysless CFTR, enabling its selective chemical modification by sulfhydryl reagents. Both cysless and wild-type CFTR ion channels have identical mean open times when activated by different nucleotide ligands. Moreover, both channels could be locked in an open state by introducing an ATPase inhibiting mutation (E1371S). However, the introduction of a single cysteine (F508C) prevented the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Chemical modification of cysless E1371S/F508C by sulfhydryl reagents was used to probe the role of the side chain in ion channel function. Specifically, benzyl-methanethiosulphonate modification of this variant restored the gating behaviour to that of cysless E1371S containing the wild-type phenylalanine at position 508. This provides the first direct evidence that a specific interaction of the Phe508 aromatic side chain plays a role in determining the residency time in the closed state. Thus, despite the fact that this aromatic side chain is not essential for CFTR folding, it is important in the ion channel function.
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.