NR AQOX
AU Shorter,J.; Lindquist,S.L.
TI Hsp104 catalyzes formation and elimination of self-replicating Sup35 prion conformers
QU Science 2004 Jun 18; 304(5678): 1793-7
PT journal article
AB The protein-remodeling factor Hsp104 governs inheritance of [PSI+], a yeast prion formed by self-perpetuating amyloid conformers of the translation termination factor Sup35. Perplexingly, either excess or insufficient Hsp104 eliminates [PSI+]. In vitro, at low concentrations, Hsp104 catalyzed the formation of oligomeric intermediates that proved critical for the nucleation of Sup 35 fibrillization de novo and displayed a conformation common among amyloidogenic polypeptides. At higher Hsp104 concentrations, amyloidogenic oligomerization and contingent fibrillization were abolished. Hsp104 also disassembled mature fibers in a manner that initially exposed new surfaces for conformational replication but eventually exterminated prion conformers. These Hsp104 activities differed in their reaction mechanism and can explain [PSI+] inheritance patterns.
MH Adenosine Triphosphate/metabolism; Adenosinetriphosphatase/metabolism; Amyloid/chemistry; Amyloid beta-Protein/chemistry/immunology; Antibodies/immunology; Biopolymers; Catalysis; Heat-Shock Proteins/chemistry/genetics/*metabolism; Hydrolysis; Mutation; Peptide Fragments/chemistry/immunology; Prions/*chemistry/*metabolism; Protein Conformation; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins/*chemistry/genetics/*metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
SP englisch
PO USA