Yeast and Fungal Prions

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Yeast and fungal prions are infectious proteins, often forming self-propagating amyloid structures from soluble proteins.
• The phenotypic effects of prions vary from mild to lethal, depending on the specific prion protein and strain.
• Prion amyloids, such as those formed by Sup35p, Ure2p, and Rnq1p, adopt in-register, parallel, folded beta-sheet architectures.

Purpose of the Study:

• To elucidate the mechanisms governing prion propagation and regulation in yeast and fungi.
• To understand the role of protein conformation templating in prion formation.
• To investigate the influence of cellular machinery, including chaperones and antiprion systems, on prion dynamics.

Main Methods:

• Analysis of prion protein structures, particularly the amyloid forms of Sup35p, Ure2p, and Rnq1p.
• Investigation of chaperone systems, including the Hsp104/Hsp70/Hsp40 complex, involved in prion propagation.
• Examination of antiprion systems like Btn2/Cur1 and Ssb in prion curing and generation blocking.

Main Results:

• Prion amyloids exhibit an in-register, parallel beta-sheet structure, facilitating conformational templating.
• Chaperone systems, notably Hsp104/Hsp70/Hsp40, are crucial for generating new prion seeds from existing filaments.
• The Btn2/Cur1 system effectively cures [URE3] prions, while the Ssb system inhibits [PSI+] prion generation.

Conclusions:

• The structural architecture of prion amyloids provides a basis for their self-templating propagation.
• Cellular chaperone and antiprion systems play critical roles in controlling the fate and propagation of yeast and fungal prions.
• Understanding these mechanisms offers insights into protein misfolding diseases and potential therapeutic targets.