[Fusion of glutathione S-transferase with the N-terminus of yeast Sup35p protein inhibits its prion-like properties].
The yeast Saccharomyces cerevisiae SUP35 gene that encodes the Sup35p protein homologous to the translation termination eRF3 factor of higher eukaryotes is essential to replication of the nonchromosomally inherited [psi+] determinant. The nonsense suppressor phenotype of this determinant was assumed to be dependent on a specific conformational state of the Sup35p protein; the transition to this state leads to partial inactivation of this protein. In terms of this hypothesis, the Sup35p protein can, like mammalian prions, induce its own specific conformation via protein-protein interactions in the newly synthesized Sup35p molecules; in this way, inheritance of the [psi+] phenotype is ensured in a series of cell generations. In recent years, this hypothesis has been experimentally verified. Allele substitution of the wild-type SUP35 gene by its chimeric GST-SUP35 version, which encodes the glutathione S-transferase sequence fused with the N end of Sup35p, was shown to cause elimination of the [psi+] determinant. The ability to eliminate [psi+] is a recessive trait, because fusions heterozygous for the GST-SUP35 allele did not lose this trait. Elimination of [psi+] seems to be caused by inability of the chimeric protein to bring about oligomerization. The obtained data indicate that the chimeric protein manifests attenuated terminating activity but can interact with the eRF1 translation termination factor encoded by the SUP45 gene.
Dagkesamanskaia
A R
AR
Kushnirov
V V
VV
Paushkin
S V
SV
Ter-Avanesian
M D
MD
D000483:Alleles; D004261:DNA Replication; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D005808:Genes, Recessive; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D010454:Peptide Termination Factors; D011328:Prions / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D013728:Terminator Regions, Genetic
D005656:Fungal Proteins; D010454:Peptide Termination Factors; D011328:Prions; D011993:Recombinant Fusion Proteins; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005982:Glutathione Transferase