The Schizosaccharomyces pombe Hsp104 disaggregase is unable to propagate the [PSI] prion.
The molecular chaperone Hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. Under stress conditions, the disaggregase activity of Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also involved in the propagation of fungal prions. For instance, the well-characterized [PSI(+)] prion of Saccharomyces cerevisiae does not propagate in Deltahsp104 cells or in cells overexpressing Hsp104. In this study, we characterized the functional homolog of Hsp104 from Schizosaccharomyces pombe (Sp_Hsp104). As its S. cerevisiae counterpart, Sp_hsp104(+) is heat-inducible and required for thermotolerance in S. pombe. Sp_Hsp104 displays low disaggregase activity and cannot propagate the [PSI(+)] prion in S. cerevisiae. When overexpressed in S. cerevisiae, Sp_Hsp104 confers thermotolerance to Deltahsp104 cells and reactivates heat-aggregated proteins. However, overexpression of Sp_Hsp104 does not propagate nor eliminate [PSI(+)]. Strikingly, [PSI(+)] was cured by overexpression of a chimeric chaperone bearing the C-terminal domain (CTD) of the S. cerevisiae Hsp104 protein. Our study demonstrates that the ability to untangle aggregated proteins is conserved between the S. pombe and S. cerevisiae Hsp104 homologs, and points to a role of the CTD in the propagation of the S. cerevisiae [PSI(+)] prion.
Sénéchal
Patrick
P
Department of Biochemistry, Université de Montréal, Montréal, Québec, Canada.
Arseneault
Geneviève
G
Leroux
Alexandre
A
Lindquist
Susan
S
Rokeach
Luis A
LA
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006358:Hot Temperature; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D010454:Peptide Termination Factors / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D013379:Substrate Specificity
D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009841:Oligonucleotides; D010454:Peptide Termination Factors; D011328:Prions; D011506:Proteins; D011993:Recombinant Fusion Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C546584:HSP104 protein, S pombe