NR AVBU
AU Shorter,J.; Lindquist,S.L.
TI Destruction or potentiation of different prions catalyzed by similar Hsp104 remodeling activities
QU Molecular Cell 2006 Aug 4; 23(3): 425-38
PT journal article
AB Yeast prions are protein-based genetic elements that self-perpetuate changes in protein conformation and function. A protein-remodeling factor, Hsp104, controls the inheritance of several yeast prions, including those formed by Sup35 and Ure2. Perplexingly, deletion of Hsp104 eliminates Sup35 and Ure2 prions, whereas overexpression of Hsp104 purges cells of Sup35 prions, but not Ure2 prions. Here, we used pure components to dissect how Hsp104 regulates prion formation, growth, and division. For both Sup35 and Ure2, Hsp104 catalyzes de novo prion nucleation from soluble, native protein. Using a distinct mechanism, Hsp104 fragments both prions to generate new prion assembly surfaces. For Sup35, the fragmentation endpoint is an ensemble of noninfectious, amyloid-like aggregates and soluble protein that cannot replicate conformation. In vivid distinction, the endpoint of Ure2 fragmentation is short prion fibers with enhanced infectivity and self-replicating ability. These advances explain the distinct effects of Hsp104 on the inheritance of the two prions.
MH Adenosine Diphosphate/chemistry; Adenosine Triphosphate/analogs & derivatives/chemistry/metabolism; Adenylyl Imidodiphosphate/chemistry; Amyloid/chemistry/metabolism/ultrastructure; Binding Sites/genetics; Catalysis; Enzyme Inhibitors/chemistry/pharmacology; Guanidine/chemistry; Heat-Shock Proteins/antagonists & inhibitors/chemistry/*metabolism; Kinetics; Microscopy, Electron, Transmission; Mutation/genetics; Prions/chemistry/*metabolism/ultrastructure; Protein Binding; Protein Conformation; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Saccharomyces cerevisiae/*enzymology/metabolism; Saccharomyces cerevisiae Proteins/antagonists &; inhibitors/chemistry/*metabolism
AD Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
SP englisch
PO USA