Mechanism of inhibition of psi + prion determinant propagation by a mutation of the N-terminus of the yeast Sup35 protein

• Published in: The EMBO journal 1998-10, Vol.17 (19), p.5805-5810
• Main Authors: Kochneva-Pervukhova, N.V, Paushkin, S.V, Kushnirov, V.V, Cox, B.S, Tuite, M.F, Ter-Avanesyan, M.D
• Format: Article
• Language: English
• Subjects: change; Chromosomes, Fungal; cytoplasmic inheritance; Fungal Proteins - genetics; Gene Dosage; inhibition; interactions; molecular conformation; mutants; Mutation; Peptide Termination Factors - genetics; polypeptide chain release factor; prion; prions; Prions - genetics; proteins; release factor eRF3; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; translation termination
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/17.19.5805

The SUP35 gene of Saccharomyces cerevisiae encodes the polypeptide chain release factor eRF3. This protein (also called Sup35p) is thought to be able to undergo a heritable conformational switch, similarly to mammalian prions, giving rise to the cytoplasmically inherited Ψ + determinant. A dominant mutation ( PNM2 allele) in the SUP35 gene causing a Gly58→Asp change in the Sup35p N‐terminal domain eliminates Ψ + . Here we observed that the mutant Sup35p can be converted to the prion‐like form in vitro , but such conversion proceeds slower than that of wild‐type Sup35p. The overexpression of mutant Sup35p induced the de novo appearance of Ψ + cells containing the prion‐like form of mutant Sup35p, which was able to transmit its properties to wild‐type Sup35p both in vitro and in vivo . Our data indicate that this Ψ + ‐eliminating mutation does not alter the initial binding of Sup35p molecules to the Sup35p Ψ + ‐specific aggregates, but rather inhibits its subsequent prion‐like rearrangement and/or binding of the next Sup35p molecule to the growing prion‐like Sup35p aggregate.