Support for the prion hypothesis for inheritance of a phenotypic trait in yeast.
A cytoplasmically inherited genetic element in yeast, [PSI+], was confirmed to be a prionlike aggregate of the cellular protein Sup35 by differential centrifugation analysis and microscopic localization of a Sup35-green fluorescent protein fusion. Aggregation depended on the intracellular concentration and functional state of the chaperone protein Hsp104 in the same manner as did [PSI+] inheritance. The amino-terminal and carboxy-terminal domains of Sup35 contributed to the unusual behavior of [PSI+]. [PSI+] altered the conformational state of newly synthesized prion proteins, inducing them to aggregate as well, thus fulfilling a major tenet of the prion hypothesis.
Patino
M M
MM
Howard Hughes Medical Institute and the Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
Liu
J J
JJ
Glover
J R
JR
Lindquist
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D005656:Fungal Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D049452:Green Fluorescent Proteins; D006360:Heat-Shock Proteins / Q000502:physiology; D008164:Luminescent Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D010641:Phenotype; D011328:Prions / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D012995:Solubility
D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D008164:Luminescent Proteins; D010454:Peptide Termination Factors; D011328:Prions; D011993:Recombinant Fusion Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D049452:Green Fluorescent Proteins