ArticleThe Journal of biological chemistry2017
Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed.
- Single-molecule dissection of CFTR folding defects and pharmacological rescue.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification and Characterization of a Rare Exon 22 Duplication inInternational journal of molecular sciences · 2025Article
- Progress of personalized medicine of cystic fibrosis in the times of efficient CFTR modulators.Molecular and cellular pediatrics · 2025Review
- Transmembrane Helices 7 and 8 Confer Aggregation Sensitivity to the Cystic Fibrosis Transmembrane Conductance Regulator.International journal of molecular sciences · 2023Article
- Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.Communications biology · 2022Article
- Stability Prediction for Mutations in the Cytosolic Domains of Cystic Fibrosis Transmembrane Conductance Regulator.Journal of chemical information and modeling · 2021Article
- Factoring in the Complexity of the Cystic Fibrosis Lung to UnderstandPathogens (Basel, Switzerland) · 2020Review
- Disease-relevant mutations alter amino acid co-evolution networks in the second nucleotide binding domain of CFTR.PloS one · 2020Article
- Hsp104 facilitates the endoplasmic-reticulum-associated degradation of disease-associated and aggregation-prone substrates.Protein science : a publication of the Protein Society · 2019Article
- Different SUMO paralogues determine the fate of wild-type and mutant CFTRs: biogenesis versus degradation.Molecular biology of the cell · 2019Article
- Structure-guided combination therapy to potently improve the function of mutant CFTRs.Nature medicine · 2018Article
- Structural analysis reveals pathomechanisms associated with pseudoxanthoma elasticum-causing mutations in the ABCC6 transporter.The Journal of biological chemistry · 2018Article
- Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.Biochimica et biophysica acta. Biomembranes · 2018Article
- ABC transportome inventory of human pathogenic yeast Candida glabrata: Phylogenetic and expression analysis.PloS one · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF.
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.