Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions
AUTOR(ES)
Parham, Steven N.
FONTE
Oxford University Press
RESUMO
The nuclear-encoded Sup35p protein is responsible for the prion-like [PSI+] determinant of yeast, with Sup35p existing largely as a high molecular weight aggregate in [PSI+] strains. Here we show that the five oligopeptide repeats present at the N-terminus of Sup35p are responsible for stabilizing aggregation of Sup35p in vivo. Sequential deletion of the oligopeptide repeats prevented the maintenance of [PSI+] by the truncated Sup35p, although deletants containing only two repeats could be incorporated into pre-existing aggregates of wild-type Sup35p. The mammalian prion protein PrP also contains similar oligopeptide repeats and we show here that a human PrP repeat (PHGGGWGQ) is able functionally to replace a Sup35p oligopeptide repeat to allow stable [PSI+] propagation in vivo. Our data suggest a model in which the oligopeptide repeats in Sup35p stabilize intermolecular interactions between Sup35p proteins that initiate establishment of the aggregated state. Modulating repeat number therefore alters the rate of yeast prion conversion in vivo. Furthermore, there appears to be evolutionary conservation of function of the N-terminally located oligopeptide repeats in prion propagation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125439Documentos Relacionados
- Interaction between yeast Sup45p (eRF1) and Sup35p (eRF3) polypeptide chain release factors: implications for prion-dependent regulation.
- Prion properties of the Sup35 protein of yeast Pichia methanolica
- Interactions of the chaperone Hsp104 with yeast Sup35 and mammalian PrP
- Importance of low-oligomeric-weight species for prion propagation in the yeast prion system Sup35/Hsp104
- Prion-inducing domain 2–114 of yeast Sup35 protein transforms in vitro into amyloid-like filaments