ArticleMolecular cell2013
Protein quality control acts on folding intermediates to shape the effects of mutations on organismal fitness.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 173 citations in OpenAlex.
- Quantifying protein unfolding kinetics with a high-throughput microfluidic platform.Cell systems · 2026Article
- Metabolite correlation networks reveal complex phenotypes of adaptation-driving mutations.Nature communications · 2026Article
- Chaperonin recognition of protein dynamics drives drug resistance.bioRxiv : the preprint server for biology · 2026Article
- Supervised learning of protein variant effects across large-scale mutagenesis datasets.Protein science : a publication of the Protein Society · 2026Article
- Conserved interfaces mediate multiple protein-protein interactions in a prokaryotic metabolon.Molecular systems biology · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning.Science advances · 2025Article
- Structural basis for anomalous cellular trafficking behavior of glaucoma-associated A427T mutant myocilin.bioRxiv : the preprint server for biology · 2025Article
- Protein Quality Control is a Master Modulator of Molecular Evolution in Bacteria.Genome biology and evolution · 2025Review
- Discovering genetic modulators of the protein homeostasis system through multilevel analysis.PNAS nexus · 2025Article
- Article
- Deep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants.Nature communications · 2024Article
- A mutational atlas for Parkin proteostasis.Nature communications · 2024Article
- Epistasis and pleiotropy shape biophysical protein subspaces associated with drug resistance.Physical review. E · 2023Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Co-translational formation of disulfides guides folding of the SARS-CoV-2 receptor binding domain.Biophysical journal · 2023Article
- Protein engineering of a nanoCLAMP antibody mimetic scaffold as a platform for producing bioprocess-compatible affinity capture ligands.The Journal of biological chemistry · 2023Article
- Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.bioRxiv : the preprint server for biology · 2023Article
- Structure, Substrate Specificity and Role of Lon Protease in Bacterial Pathogenesis and Survival.International journal of molecular sciences · 2023Review
- Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
What are the molecular properties of proteins that fall on the radar of protein quality control (PQC)? Here we mutate the E. coli's gene encoding dihydrofolate reductase (DHFR) and replace it with bacterial orthologous genes to determine how components of PQC modulate fitness effects of these genetic changes. We find that chaperonins GroEL/ES and protease Lon compete for binding to molten globule intermediate of DHFR, resulting in a peculiar symmetry in their action: overexpression of GroEL/ES and deletion of Lon both restore growth of deleterious DHFR mutants and most of the slow-growing orthologous DHFR strains. Kinetic steady-state modeling predicts and experimentation verifies that mutations affect fitness by shifting the flux balance in cellular milieu between protein production, folding, and degradation orchestrated by PQC through the interaction with folding intermediates.
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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.