ArticleCommunications biology2022
Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Article
- 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
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- Proteostasis Landscapes of Cystic Fibrosis Variants Reveals Drug Response Vulnerability.bioRxiv : the preprint server for biology · 2025Article
- COPII cage assembly factor Sec13 integrates information flow regulating endomembrane function in response to human variation.Scientific reports · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Benchmarking AlphaMissense Pathogenicity Predictions Against Cystic Fibrosis Variants.bioRxiv : the preprint server for biology · 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
- Understanding the host-pathogen evolutionary balance through Gaussian process modeling of SARS-CoV-2.Patterns (New York, N.Y.) · 2023Article
- Rescue of Rare CFTR Trafficking Mutants Highlights a Structural Location-Dependent Pattern for Correction.International journal of molecular sciences · 2023Article
- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis.Cell chemical biology · 2023Article
- Triangulating variation in the population to define mechanisms for precision management of genetic disease.Structure (London, England : 1993) · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors.
Funding
Abstract
Although the impact of genome variation on the thermodynamic properties of function on the protein fold has been studied in vitro, it remains a challenge to assign these relationships across the entire polypeptide sequence in vivo. Using the Gaussian process regression based principle of Spatial CoVariance, we globally assign on a residue-by-residue basis the biological thermodynamic properties that contribute to the functional fold of CFTR in the cell. We demonstrate the existence of a thermodynamically sensitive region of the CFTR fold involving the interface between NBD1 and ICL4 that contributes to its export from endoplasmic reticulum. At the cell surface a new set of residues contribute uniquely to the management of channel function. These results support a general 'quality assurance' view of global protein fold management as an SCV principle describing the differential pre- and post-ER residue interactions contributing to compartmentalization of the energetics of the protein fold for function. Our results set the stage for future analyses of the quality systems managing protein sequence-to-function-to-structure broadly encompassing genome design leading to protein function in complex cellular relationships responsible for diversity and fitness in biology in response to the environment.
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