The Sup35 domains required for maintenance of weak, strong or undifferentiated yeast [PSI+] prions

Area of Science:

• Protein biochemistry
• Prion biology
• Molecular genetics

Background:

• The Sup35 protein forms infectious prion variants known as [PSI+].
• Prion domains are minimal protein fragments maintaining prion forms.
• The Sup35 N-terminal region (residues 1-123) is often considered the prion domain.

Purpose of the Study:

• To investigate the minimal region of Sup35 required for maintaining distinct [PSI+] prion variants.
• To determine the sufficiency of the N-terminal region (1-123) for prion variant stability.
• To identify specific residues involved in variant-specific prion maintenance.

Main Methods:

• In vitro assays using Sup35 protein fragments.
• Analysis of prion variant stability and differentiation.
• Computational structure prediction of Sup35 regions.

Main Results:

• The Sup35 N-terminal region (residues 1-123) is insufficient to maintain weak or strong [PSI+] variants independently.
• Residues 1-123 maintain an 'undifferentiated' [PSI+] state that requires full-length Sup35 for differentiation.
• Sup35 residues 1-137 are necessary and sufficient for maintaining both weak and strong [PSI+] variants.
• Residues 124-137 are implicated in the variant-specific maintenance of [PSI+] forms.
• Structural predictions suggest alpha-helical structure for residues 124-137 and potential beta-structure for residues 1-123.

Conclusions:

• The definition of a 'prion domain' requires re-evaluation based on variant-specific maintenance.
• Residues 124-137 of Sup35 play a critical role in the stability and specificity of [PSI+] prion variants.
• These findings provide insights into the molecular basis of prion strain diversity.