title: Methionine oxidation of Sup35 protein induces formation of the [PSI+] prion in a yeast peroxiredoxin mutant.
abstract: The frequency with which the yeast [PSI(+)] prion form of Sup35 arises de novo is controlled by a number of genetic and environmental factors. We have previously shown that in cells lacking the antioxidant peroxiredoxin proteins Tsa1 and Tsa2, the frequency of de novo formation of [PSI(+)] is greatly elevated. We show here that Tsa1/Tsa2 also function to suppress the formation of the [PIN(+)] prion form of Rnq1. However, although oxidative stress increases the de novo formation of both [PIN(+)] and [PSI(+)], it does not overcome the requirement of cells being [PIN(+)] to form the [PSI(+)] prion. We use an anti-methionine sulfoxide antibody to show that methionine oxidation is elevated in Sup35 during oxidative stress conditions. Abrogating Sup35 methionine oxidation by overexpressing methionine sulfoxide reductase (MSRA) prevents [PSI(+)] formation, indicating that Sup35 oxidation may underlie the switch from a soluble to an aggregated form of Sup35. In contrast, we were unable to detect methionine oxidation of Rnq1, and MSRA overexpression did not affect [PIN(+)] formation in a tsa1 tsa2 mutant. The molecular basis of how yeast and mammalian prions form infectious amyloid-like structures de novo is poorly understood. Our data suggest a causal link between Sup35 protein oxidation and de novo [PSI(+)] prion formation.
authors.affiliation: Faculty of Life Sciences, University of Manchester, the Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom.
authors.forename: Theodora C
authors.initials: TC
authors.lastname: Sideri
authors.forename: Nadejda
authors.initials: N
authors.lastname: Koloteva-Levine
authors.forename: Mick F
authors.initials: MF
authors.lastname: Tuite
authors.forename: Chris M
authors.initials: CM
authors.lastname: Grant
mesh_terms: D008715:Methionine / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010454:Peptide Termination Factors / Q000235:genetics / Q000378:metabolism*; D010544:Peroxidases; D054464:Peroxiredoxins; D011328:Prions / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D010454:Peptide Termination Factors; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008715:Methionine; D010088:Oxidoreductases; D010544:Peroxidases; C496253:Tsa1 protein, S cerevisiae; C496254:Tsa2 protein, S cerevisiae; D054464:Peroxiredoxins; C487504:MsrA protein, S cerevisiae