ArticleBiomolecules2022
Structural Comparative Modeling of Multi-Domain F508del CFTR.
Article in Biomolecules, 2022. 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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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.
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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.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Profiling the CFTR Variant Selectivity and Off-Target Interactions of VX-121.bioRxiv : the preprint server for biology · 2026Article
- General trends in the calnexin-dependent expression and pharmacological rescue of clinical CFTR variants.eLife · 2025Article
- Targeting the Aryl Hydrocarbon Receptor: The Potential of Indole Compounds in the Treatment of Cystic Fibrosis.International journal of molecular sciences · 2025Review
- General Trends in the Calnexin-Dependent Expression and Pharmacological Rescue of Clinical CFTR Variants.bioRxiv : the preprint server for biology · 2025Article
- Recent developments in cystic fibrosis drug discovery: where are we today?Expert opinion on drug discovery · 2025Review
- Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Proteostasis Landscapes of Cystic Fibrosis Variants Reveals Drug Response Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Identification of novel natural compounds against CFTR p.Gly628Arg pathogenic variant.AMB Express · 2024Article
- Benchmarking AlphaMissense Pathogenicity Predictions Against Cystic Fibrosis Variants.bioRxiv : the preprint server for biology · 2024Article
- Dark nanodiscs for evaluating membrane protein thermostability by differential scanning fluorimetry.Biophysical journal · 2024Article
- Benchmarking AlphaMissense pathogenicity predictions against cystic fibrosis variants.PloS one · 2024Article
- CFTR Folding: From Structure and Proteostasis to Cystic Fibrosis Personalized Medicine.ACS chemical biology · 2023Review
- Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs.Biochemistry · 2023Article
- General trends in the effects of VX-661 and VX-445 on the plasma membrane expression of clinical CFTR variants.Cell chemical biology · 2023Article
- Computational modeling and prediction of deletion mutants.Structure (London, England : 1993) · 2023Article
- Benchmarking AlphaFold2 on peptide structure prediction.Structure (London, England : 1993) · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Cystic fibrosis (CF) is a rare genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial anion channel expressed in several vital organs. Absence of functional CFTR results in imbalanced osmotic equilibrium and subsequent mucus build up in the lungs-which increases the risk of infection and eventually causes death. CFTR is an ATP-binding cassette (ABC) transporter family protein composed of two transmembrane domains (TMDs), two nucleotide binding domains (NBDs), and an unstructured regulatory domain. The most prevalent patient mutation is the deletion of F508 (F508del), making F508del CFTR the primary target for current FDA approved CF therapies. However, no experimental multi-domain F508del CFTR structure has been determined and few studies have modeled F508del using multi-domain WT CFTR structures. Here, we used cryo-EM density data and Rosetta comparative modeling (RosettaCM) to compare a F508del model with published experimental data on CFTR NBD1 thermodynamics. We then apply this modeling method to generate multi-domain WT and F508del CFTR structural models. These models demonstrate the destabilizing effects of F508del on NBD1 and the NBD1/TMD interface in both the inactive and active conformation of CFTR. Furthermore, we modeled F508del/R1070W and F508del bound to the CFTR corrector VX-809. Our models reveal the stabilizing effects of VX-809 on multi-domain models of F508del CFTR and pave the way for rational design of additional drugs that target F508del CFTR for treatment of CF.
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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.