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Mechanism of inhibition of Ψ + prion determinant propagation by a mutation of the N‐terminus of the yeast Sup35 protein
Author(s) -
KochnevaPervukhova Natalia V.,
Paushkin Sergey V.,
Kushnirov Vitaly V.,
Cox Brian S.,
Tuite Mick F.,
TerAvanesyan Michael D.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.19.5805
Subject(s) - biology , mutation , mechanism (biology) , yeast , saccharomyces cerevisiae , genetics , fungal protein , plasma protein binding , prion protein , microbiology and biotechnology , biochemistry , gene , medicine , philosophy , disease , epistemology , pathology
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.