Prions are conformationally flexible proteins capable of adopting a native state and a spectrum of alternative states associated with a change in the function of the protein. These alternative states are prone to assemble into amyloid aggregates, which provide a structure for self-replication and transmission of the underlying conformer and thereby the emergence of a new phenotype. Amyloid appearance is a rare event in vivo, regulated by both the aggregation propensity of prion proteins and their cellular environment. How these forces normally intersect to suppress amyloid appearance and the ways in which these restrictions can be bypassed to create protein-only phenotypes remain poorly understood. The most widely studied and perhaps most experimentally tractable system to explore the mechanisms regulating amyloid appearance is the [PIN+] prion of Saccharomyces cerevisiae. [PIN+] is required for the appearance of the amyloid state for both native yeast proteins and for human proteins expressed in yeast. These observations suggest that [PIN+] facilitates the bypass of amyloid regulatory mechanisms by other proteins in vivo. Several models of prion appearance are compatible with current observations, highlighting the complexity of the process and the questions that must be resolved to gain greater insight into the mechanisms regulating these events.

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Journal Article | Research Support, N.I.H., Extramural | Review

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Serio TR

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