A Size Threshold Limits Prion Transmission and Establishes Phenotypic Diversity
Year: 2010
Type: article
Abstract: According to the prion hypothesis, atypical phenotypes arise when a prion protein adopts an alternative conformation and persist when that form assembles into self-replicating aggregates. Amyloid formation in vitro provides a model for this protein-misfolding pathway, but the mechanism by which this process interacts with the cellular environment to produce transmissible phenotypes is poorly understood. Using the yeast prion Sup35/[PSI(+)], we found that protein conformation determined the size distribution of aggregates through its interactions with a molecular chaperone. Shifts in this range created variations in aggregate abundance among cells because of a size threshold for transmission, and this heterogeneity, along with aggregate growth and fragmentation, induced age-dependent fluctuations in phenotype. Thus, prion conformations may specify phenotypes as population averages in a dynamic system.
Source: Science
Institution: Brown University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Investigating the Mechanism of Sup35 Prion Curing by Excess Hsp104, Investigating the Mechanism of Prion Curing by [PSI+] No More Mutations, Training in Molecular and Cell Biology and Biochemistry, Modeling Prion Dynamics, Role of the Actin Cytoskeleton in Yeast Prion Propagation, Prion Cycle Regulation In Vivo
OpenAlex ID: W2036404841