Origins and kinetic consequences of diversity in Sup35 yeast prion fibers.
A remarkable feature of prions is that infectious particles composed of the same prion protein can give rise to different phenotypes. This strain phenomenon suggests that a single prion protein can adopt multiple infectious conformations. Here we use a novel single fiber growth assay to examine the heterogeneity of amyloid fibers formed by the yeast Sup35 prion protein. Sup35 spontaneously forms multiple, distinct and faithfully propagating fiber types, which differ dramatically both in their degrees of polarity and overall growth rates. Both in terms of the number of distinct self-propagating fiber types, as well as the ability of these differences to dictate the rate of prion growth, this diversity is well suited to account for the range of prion strain phenotypes observed in vivo.
DePace
Angela H
AH
Howard Hughes Medical Institute and Department of Cellular Pharmacology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California, 94143-0450, USA.
Weissman
Jonathan S
JS
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D018625:Microscopy, Atomic Force; D010454:Peptide Termination Factors; D011328:Prions / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D020836:Protein Structure, Quaternary; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000737:chemistry*
D000682:Amyloid; D005656:Fungal Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins