Prion protein remodelling confers an immediate phenotypic switch

Area of Science:

• Molecular Biology
• Protein Biochemistry
• Yeast Genetics

Background:

• Proteins, termed prions, can adopt multiple functional states in vivo, influencing processes like inheritance.
• Newly synthesized prion proteins typically adopt the existing cellular conformation, ensuring faithful phenotypic transmission.
• The mechanisms governing phenotypic switching and the fate of existing proteins during these transitions remain unclear.

Purpose of the Study:

• To investigate the protein-state changes that trigger phenotypic switching in the yeast prion Sup35/[PSI(+)].
• To determine if prion formation requires a specific misfolding pathway during protein synthesis or can occur in mature proteins.

Main Methods:

• Analysis of protein-state transitions in yeast Sup35/[PSI(+)].
• Investigating the role of mature protein remodeling in prion-induced phenotypic changes.

Main Results:

• The prion form of Sup35 does not require a de novo misfolding pathway during synthesis.
• Mature Sup35 protein can access the prion state through remodelling.
• This transition is associated with a loss of Sup35 activity, leading to rapid cellular phenotype alteration.

Conclusions:

• Phenotypic switching in yeast prions can be initiated by changes in mature protein conformation.
• The remodelling of existing Sup35 protein drives rapid phenotypic changes within a single cell cycle.
• This finding offers new insights into prion biology and protein-based inheritance mechanisms.