NR ALWA
AU Uptain,S.M.; Sawicki,G.J.; Caughey,B.W.; Lindquist,S.L.
TI Strains of [PSI(+)] are distinguished by their efficiencies of prion-mediated conformational conversion
QU EMBO Journal 2001 Nov 15; 20(22): 6236-45
PT journal article
AB Yeast prions are protein-based genetic elements that produce phenotypes through self-perpetuating changes in protein conformation. For the prion [PSI(+)] this protein is Sup35, which is comprised of a prion-determining region (NM) fused to a translational termination region. [PSI(+)] strains (variants) with different heritable translational termination defects (weak or strong) can exist in the same genetic background. [PSI(+)] variants are reminiscent of mammalian prion strains, which can be passaged in the same mouse strain yet have different disease latencies and brain pathologies. We found that [PSI(+)] variants contain different ratios of Sup35 in the prion and non-prion state that correlate with different translation termination efficiencies. Indeed, the partially purified prion form of Sup35 from a strong [PSI(+)] variant converted purified NM much more efficiently than that of several weak variants. However, this difference was lost in a second round of conversion in vitro. Thus, [PSI(+)] variants result from differences in the efficiency of prion-mediated conversion, and the maintenance of [PSI(+)] variants involves more than nucleated conformational conversion (templating) to NM alone.
MH Brain/metabolism; Cell Nucleus/metabolism; Dose-Response Relationship, Drug; Fungal Proteins/*biosynthesis/chemistry/*genetics; Immunoblotting; Lyases/chemistry; Phenotype; Prions/chemistry; Protein Conformation; Recombinant Fusion Proteins/metabolism; Recombinant Proteins/chemistry; Spectroscopy, Fourier Transform Infrared; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Translation, Genetic
AD Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
SP englisch
PO England