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Prions in Saccharomyces and Podospora spp.: protein-based inheritance
R B Wickner1, K L Taylor, H K Edskes
1Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0830, USA. wickner@helix.nih.gov
Microbiology and Molecular Biology Reviews : MMBR
|December 10, 1999
Summary
Prions, infectious proteins like [URE3] and [PSI] in yeast, and [Het-s] in fungi, control cellular functions. These protein aggregates, similar to those in diseases like Alzheimer's, can be studied and potentially manipulated.
Area of Science:
- Molecular Biology
- Mycology
- Neuroscience
Background:
- Non-Mendelian genetic elements [URE3] and [PSI] in Saccharomyces cerevisiae identified as prions of Ure2p and Sup35p.
- Prions are self-propagating protein aggregates, with amyloid structures characteristic of diseases like Alzheimer's and transmissible spongiform encephalopathies.
- The filamentous fungus Podospora anserina possesses a prion element [Het-s] of the het-s protein, essential for heterokaryon incompatibility.
Purpose of the Study:
- To investigate the nature and function of prions in yeast and fungi.
- To explore the structural and functional similarities between fungal prions and human disease-associated protein aggregates.
- To identify key domains and factors involved in prion formation and propagation.
Main Methods:
- Genetic analysis to identify prion elements and their corresponding proteins.
- In vitro studies of protein aggregation, including amyloid formation and Congo Red staining.
- Investigating the role of specific protein domains (e.g., Asn/Gln-rich regions) in prion formation.
- Assessing the impact of chaperone proteins (Hsp104) and chemical agents (guanidine HCl) on prion propagation.
Main Results:
- [URE3] and [PSI] prions involve self-propagating aggregation of Ure2p and Sup35p, forming amyloid structures.
- [URE3] controls nitrogen catabolism, while [PSI] affects tRNA suppression efficiency.
- The prion domain of Ure2p is Asn-rich (residues 1-80); Sup35 prion domain is Asn/Gln-rich (residues 1-114).
- Overproduction of Ure2p fragments can induce de novo [URE3] formation.
- Hsp104 levels affect [PSI] propagation; guanidine HCl cures both [URE3] and [PSI].
Conclusions:
- Prions are functional elements in yeast and fungi, controlling essential cellular processes.
- Prion formation involves specific protein domains and can be influenced by cellular chaperones and environmental factors.
- Understanding fungal prions provides insights into protein misfolding diseases like Alzheimer's and prion diseases.