ArticlePLoS genetics2013
Latent effects of Hsp90 mutants revealed at reduced expression levels.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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
65 citing papers in PubMed.
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
- Article
- Mutational scan of self-cleavage by HIV-1 protease provides new views of a conformationally dynamic mechanism.Journal of virology · 2026Article
- Mutational scan of self-cleavage by HIV-1 protease provides new views of a conformationally dynamic mechanism.bioRxiv : the preprint server for biology · 2025Article
- Epitope mapping via in vitro deep mutational scanning methods and its applications.The Journal of biological chemistry · 2025Review
- Dominant negative mutations in yeast Hsp90 indicate triage decision mechanism targeting client proteins for degradation.Molecular biology of the cell · 2025Article
- Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.Molecular biology and evolution · 2024Article
- Dominant negative mutations in yeast Hsp90 reveal triage decision mechanism targeting client proteins for degradation.bioRxiv : the preprint server for biology · 2024Article
- Contributions of Hyperactive Mutations in MACS infectious diseases · 2024Article
- Insights into Hsp90 mechanism andFrontiers in molecular biosciences · 2024Review
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- Nucleotide exchange is sufficient for Hsp90 functions in vivo.Nature communications · 2023Article
- Fitness and Functional Landscapes of the E. coli RNase III Gene rnc.Molecular biology and evolution · 2023Article
- Mutational scan inferred binding energetics and structure in intrinsically disordered protein CcdA.Protein science : a publication of the Protein Society · 2023Article
- Epistasis between promoter activity and coding mutations shapes gene evolvability.Science advances · 2023Article
- Mutational fitness landscape and drug resistance.Current opinion in structural biology · 2023Review
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
- Translational reprogramming in response to accumulating stressors ensures critical threshold levels of Hsp90 for mammalian life.Nature communications · 2022Article
- The High Mutational Sensitivity of ccdA Antitoxin Is Linked to Codon Optimality.Molecular biology and evolution · 2022Article
5 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.
Funding
Abstract
In natural systems, selection acts on both protein sequence and expression level, but it is unclear how selection integrates over these two dimensions. We recently developed the EMPIRIC approach to systematically determine the fitness effects of all possible point mutants for important regions of essential genes in yeast. Here, we systematically investigated the fitness effects of point mutations in a putative substrate binding loop of yeast Hsp90 (Hsp82) over a broad range of expression strengths. Negative epistasis between reduced expression strength and amino acid substitutions was common, and the endogenous expression strength frequently obscured mutant defects. By analyzing fitness effects at varied expression strengths, we were able to uncover all mutant effects on function. The majority of mutants caused partial functional defects, consistent with this region of Hsp90 contributing to a mutation sensitive and critical process. These results demonstrate that important functional regions of proteins can tolerate mutational defects without experimentally observable impacts on fitness.
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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.