title: Expanding the yeast prion world: Active prion conversion of non-glutamine/asparagine-rich Mod5 for cell survival.
abstract: Mammalian and fungal prion proteins form self-perpetuating β-sheet-rich fibrillar aggregates called amyloid. Prion inheritance is based on propagation of the regularly oriented amyloid structures of the prion proteins. All yeast prion proteins identified thus far contain aggregation-prone glutamine/asparagine (Gln/Asn)-rich domains, although the mammalian prion protein and fungal prion protein HET-s do not contain such sequences. In order to fill this gap, we searched for novel yeast prion proteins lacking Gln/Asn-rich domains via a genome-wide screen based on cross-seeding between two heterologous proteins and identified Mod5, a yeast tRNA isopentenyltransferase, as a novel non-Gln/Asn-rich yeast prion protein. Mod5 formed self-propagating amyloid fibers in vitro and the introduction of Mod5 amyloids into non-prion yeast induced dominantly and cytoplasmically heritable prion state [MOD (+) ], which harbors aggregates of endogenous Mod5. [MOD (+) ] yeast showed an increased level of membrane lipid ergosterol and acquired resistance to antifungal agents. Importantly, enhanced de novo formation of [MOD (+) ] was observed when non-prion yeast was grown under selective pressures from antifungal drugs. Our findings expand the family of yeast prions to non-Gln/Asn-rich proteins and reveal the acquisition of a fitness advantage for cell survival through active prion conversion.
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Genjiro
authors.initials: G
authors.lastname: Suzuki
authors.forename: Motomasa
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D000935:Antifungal Agents / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016681:Genome, Fungal; D050296:Microbial Viability; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; D000935:Antifungal Agents; D005656:Fungal Proteins; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D019883:Alkyl and Aryl Transferases; C068392:MOD5 protein, S cerevisiae; C023197:tRNA isopentenyltransferase
keywords: Mod5; amyloid; antifungal drug; cellular adaptation; prion; tRNA isopentenyltransferase