1 Unraveling Infectious Structures, Strain Variants and Species Barriers for the Yeast Prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is β-sheet rich, infectious and self-perpetuating in nature. These infectious proteins display several remarkable biological activities, including the ability to form multiple infectious prion conformations (also known as strains or variants) that encode unique biological phenotypes, and the ability to establish and overcome prion species (transmission) barriers. In this review, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher these biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and propose approaches to accelerate the understanding of these enigmatic, infectious conformers.