New Publication for the True Lab.
Congratulations to Laura Westergard and Heather True!
Westergard, L. and True, H.L. (2014) Extracellular envionment modulates the formation and propagation of particular amyloid structures. Mol. Microbiol. [E-published March 17]
Abstract: Amyloidogenic proteins, including prions, assemble into multiple forms of structurally-distinct fibers. The [PSI+ ] prion, endogenous to the yeast Saccharomyces cerevisiae, is a dominantly inherited, epigenetic modifier of phenotypes. [PSI+ ] formation relies on the coexistence of another prion, [RNQ+ ]. Here, in order to better define the role of amyloid diversity on cellular phenotypes, we investigated how physiological and environmental changes impact the generation and propagation of diverse protein conformations from a single polypeptide. Utilizing the yeast model system, we defined extracellular factors that influence the formation of a spectrum of alternative self-propagating amyloid structures of the Sup35 protein, called [PSI+ ] variants. Strikingly, exposure to specific stressful environments dramatically altered the variants of [PSI+ ] that formed de novo. Additionally, we found that stress also influenced the association between the [PSI+ ] and [RNQ+ ] prions in a way that it superceded their typical relationship. Furthermore, changing the growth environment modified both the biochemical properties and [PSI+ ]-inducing capabilities of the [RNQ+ ] template. These data suggest that the cellular environment contributes to both the generation and the selective propagation of specific amyloid structures, providing insight into a key feature that impacts phenotypic diversity in yeast and the cross-species transmission barriers characteristic of prion diseases.
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