Hsp104 Catalyzes Formation and Elimination of Self-Replicating Sup35 Prion Conformers
2004; American Association for the Advancement of Science; Volume: 304; Issue: 5678 Linguagem: Inglês
10.1126/science.1098007
ISSN1095-9203
AutoresJames Shorter, Susan Lindquist,
Tópico(s)Neurological diseases and metabolism
ResumoThe 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.
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