ArticlePLoS genetics2017
A dominant-negative mutant inhibits multiple prion variants through a common mechanism.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Multiple aspects of amyloid dynamicsFrontiers in molecular neuroscience · 2024Article
- Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures.Viruses · 2022Review
- A structured model and likelihood approach to estimate yeast prion propagon replication rates and their asymmetric transmission.PLoS computational biology · 2022Article
- AAA+ proteins: one motor, multiple ways to work.Biochemical Society transactions · 2022Review
- Nucleation seed size determines amyloid clearance and establishes a barrier to prion appearance in yeast.Nature structural & molecular biology · 2020Article
- A unifying model for the propagation of prion proteins in yeast brings insight into the [PSI+] prion.PLoS computational biology · 2020Article
- Engineered protein disaggregases mitigate toxicity of aberrant prion-like fusion proteins underlying sarcoma.The Journal of biological chemistry · 2019Article
- Design of a New [Frontiers in molecular neuroscience · 2019Article
- Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain.FEMS yeast research · 2018Article
- Prion Replication in the Mammalian Cytosol: Functional Regions within a Prion Domain Driving Induction, Propagation, and Inheritance.Molecular and cellular biology · 2018Article
- [PIN+]ing down the mechanism of prion appearance.FEMS yeast research · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.
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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.