The role of Sis1 in the maintenance of the [RNQ+] prion.
Yeast prions are inherited through proteins that exist in alternate, self-perpetuating conformational states. The mechanisms by which these states arise and are maintained are still poorly defined. Here we demonstrate for the first time that Sis1, a member of the Hsp40 chaperone family, plays a critical role in the maintenance of a prion. The prion [RNQ+] is formed by Rnq1, which is present in the same physical complex as Sis1, but only when Rnq1 is in the prion state. The G/F domain of Sis1 is dispensable for rapid growth on rich medium, but is required for [RNQ+] maintenance, distinguishing essential regions of Sis1 from those needed for prion interaction. A specific Sis1 deletion mutant altered the physical aggregation pattern of Rnq1 without curing the prion. This variant state propagated in a heritable fashion after wild-type Sis1 function was restored, indicating that multiple physical states are compatible with prion maintenance and that changes in chaperone activity can create prion variants. Using a prion chimera we demonstrate that the prion-determinant domain of Rnq1 is genetically sufficient for control by Sis1.
Sondheimer
N
N
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, 5841 S. Maryland Avenue MC1028, Chicago, IL 60637, USA.
Lopez
N
N
Craig
E A
EA
Lindquist
S
S
D000251:Adenosine Triphosphatases; D005656:Fungal Proteins / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D016296:Mutagenesis; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008164:Luminescent Proteins; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; C070320:SIS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae