ArticlePLoS pathogens2009
Trans-dominant inhibition of prion propagation in vitro is not mediated by an accessory cofactor.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Prion protein E219K polymorphism: from the discovery of the KANNO blood group to interventions for human prion disease.Frontiers in neurology · 2024Review
- Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.Science translational medicine · 2022Article
- Structural effects of the highly protective V127 polymorphism on human prion protein.Communications biology · 2020Article
- Diverse, evolving conformer populations drive distinct phenotypes in frontotemporal lobar degeneration caused by the same MAPT-P301L mutation.Acta neuropathologica · 2020Article
- Alteration of Prion Strain Emergence by Nonhost Factors.mSphere · 2019Article
- A Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models.Molecular neurobiology · 2019Article
- Engineering a murine cell line for the stable propagation of hamster prions.The Journal of biological chemistry · 2019Article
- In vitro Modeling of Prion Strain Tropism.Viruses · 2019Review
- An Amino Acid Substitution Found in Animals with Low Susceptibility to Prion Diseases Confers a Protective Dominant-Negative Effect in Prion-Infected Transgenic Mice.Molecular neurobiology · 2018Article
- A dominant-negative mutant inhibits multiple prion variants through a common mechanism.PLoS genetics · 2017Article
- Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases.Methods in molecular biology (Clifton, N.J.) · 2017Review
- Interallelic Transcriptional Enhancement as an in Vivo Measure of Transvection in Drosophila melanogaster.G3 (Bethesda, Md.) · 2016Article
- Human prion protein sequence elements impede cross-species chronic wasting disease transmission.The Journal of clinical investigation · 2015Article
- Requirements for mutant and wild-type prion protein misfolding in vitro.Biochemistry · 2015Article
- Article
- A proposed mechanism for the promotion of prion conversion involving a strictly conserved tyrosine residue in the β2-α2 loop of PrPC.The Journal of biological chemistry · 2014Article
- Prion transmission prevented by modifying the β2-α2 loop structure of host PrPC.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- De novo generation of infectious prions with bacterially expressed recombinant prion protein.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Recombinant human prion protein inhibits prion propagation in vitro.Scientific reports · 2013Article
- Probing early misfolding events in prion protein mutants by NMR spectroscopy.Molecules (Basel, Switzerland) · 2013Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies identified prion protein (PrP) mutants which act as dominant negative inhibitors of prion formation through a mechanism hypothesized to require an unidentified species-specific cofactor termed protein X. To study the mechanism of dominant negative inhibition in vitro, we used recombinant PrP(C) molecules expressed in Chinese hamster ovary cells as substrates in serial protein misfolding cyclic amplification (sPMCA) reactions. Bioassays confirmed that the products of these reactions are infectious. Using this system, we find that: (1) trans-dominant inhibition can be dissociated from conversion activity, (2) dominant-negative inhibition of prion formation can be reconstituted in vitro using only purified substrates, even when wild type (WT) PrP(C) is pre-incubated with poly(A) RNA and PrP(Sc) template, and (3) Q172R is the only hamster PrP mutant tested that fails to convert into PrP(Sc) and that can dominantly inhibit conversion of WT PrP at sub-stoichiometric levels. These results refute the hypothesis that protein X is required to mediate dominant inhibition of prion propagation, and suggest that PrP molecules compete for binding to a nascent seeding site on newly formed PrP(Sc) molecules, most likely through an epitope containing residue 172.
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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.