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Updated: May 23, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Probing the role of structural features of mouse PrP in yeast by expression as Sup35-PrP fusions
Lyne Jossé1, Ricardo Marchante, Jo Zenthon
1Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, UK.
Abstract:
The yeast Saccharomyces cerevisiae is a tractable model organism in which both to explore the molecular mechanisms underlying the generation of disease-associated protein misfolding and to map the cellular responses to potentially toxic misfolded proteins. Specific targets have included proteins which in certain disease states form amyloids and lead to neurodegeneration. Such studies are greatly facilitated by the extensive 'toolbox' available to the yeast researcher that provides a range of cell engineering options. Consequently, a number of assays at the cell and molecular level have been set up to report on specific protein misfolding events associated with endogenous or heterologous proteins. One major target is the mammalian prion protein PrP because we know little about what specific sequence and/or structural feature(s) of PrP are important for its conversion to the infectious prion form, PrP (Sc) . Here, using a study of the expression in yeast of fusion proteins comprising the yeast prion protein Sup35 fused to various regions of mouse PrP protein, we show how PrP sequences can direct the formation of non-transmissible amyloids and focus in particular on the role of the mouse octarepeat region. Through this study we illustrate the benefits and limitations of yeast-based models for protein misfolding disorders.
Insights
Yeast models reveal how prion protein (PrP) sequences, particularly the octarepeat region, can drive amyloid formation. This study highlights yeast
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Yeast, particularly Saccharomyces cerevisiae, serves as a model organism for studying protein misfolding diseases.
- Misfolded proteins, such as amyloids, are implicated in neurodegenerative conditions.
- Understanding the mechanisms of protein misfolding is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of specific prion protein (PrP) sequences in amyloid formation using a yeast-based system.
- To identify sequence and structural features of PrP critical for its conversion into an infectious form.
- To explore the utility of yeast as a model for studying protein misfolding disorders.
Main Methods:
- Expression of fusion proteins in yeast (Saccharomyces cerevisiae) comprising Sup35 and various regions of mouse PrP.
- Utilizing yeast-based assays to detect and analyze protein misfolding events.
- Focusing on the contribution of the mouse octarepeat region in PrP-induced amyloidogenesis.
Main Results:
- Prion protein (PrP) sequences can direct the formation of non-transmissible amyloids in yeast.
- The mouse octarepeat region of PrP plays a significant role in this amyloid formation.
- Demonstrated the capacity of yeast models to study specific aspects of PrP misfolding.
Conclusions:
- Yeast models are valuable tools for dissecting the molecular basis of protein misfolding disorders.
- Specific PrP regions, like the octarepeat, can induce amyloid formation independently of the infectious prion form.
- The study underscores both the strengths and limitations of using yeast for modeling human protein misfolding diseases.
