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Prion. 2013 Mar-Apr;7(2):109-13. doi: 10.4161/pri.22685. Epub 2012 Nov 1.

Expanding the yeast prion world: Active prion conversion of non-glutamine/asparagine-rich Mod5 for cell survival.

Author information

1
Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama, Japan.

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.

KEYWORDS:

Mod5; amyloid; antifungal drug; cellular adaptation; prion; tRNA isopentenyltransferase

PMID:
23117914
PMCID:
PMC3609114
DOI:
10.4161/pri.22685
[Indexed for MEDLINE]
Free PMC Article

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