NR AGPZ
AU Kochneva-Pervukhova,N.V.; Paushkin,S.V.; Kushnirov,V.V.; Cox,B.S.; Tuite,M.F.; Ter-Avanesyan,M.D.
TI Mechanism of inhibition of Psi+ prion determinant propagation by a mutation of the N-terminus of the yeast Sup35 protein
QU EMBO Journal 1998 Oct 1; 17(19): 5805-10
PT journal article
AB 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 Psi+ determinant. A dominant mutation (PNM2 allele) in the SUP35 gene causing a Gly58 -> Asp change in the Sup35p N-terminal domain eliminates Psi+. 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 Psi+ 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 Psi+-eliminating mutation does not alter the initial binding of Sup35p molecules to the Sup35p Psi+-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.
MH Chromosomes, Fungal; Fungal Proteins/*genetics; Gene Dosage; *Mutation; Peptide Termination Factors/genetics; Prions/*genetics; Saccharomyces cerevisiae/*genetics; Support, Non-U.S. Gov't
AD Institute of Experimental Cardiology, Cardiology Research Center, 3rd Cherepkovskaya Street 15A, Moscow 121552, Russia.
SP englisch
PO England