[PHI+], a novel Sup35‐prion variant propagated with non‐Gln/Asn oligopeptide repeats in the absence of the chaperone protein Hsp104

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2003-07, Vol.8 (7), p.603-618
• Main Authors: Crist, Colin G., Nakayashiki, Toru, Kurahashi, Hiroshi, Nakamura, Yoshikazu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Asparagine - chemistry; Base Sequence; DNA Primers; Glycine - chemistry; Heat-Shock Proteins - metabolism; Molecular Sequence Data; Peptide Termination Factors; Prions - chemistry; Prions - genetics; Prions - metabolism; Repetitive Sequences, Amino Acid; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1046/j.1365-2443.2003.00661.x

Background: The [PSI+] element of the budding yeast is an aggregated form of the translation release factor Sup35 that is propagated and transmitted cytoplasmically in a manner analogous to that of mammalian prions. The N‐terminal of Sup35, necessary for [PSI+], contains oligopeptide repeats and multiple Gln/Asn residues. Results: We replaced the Gln/Asn‐rich prion repeats of Sup35 with non‐Gln/Asn repeats from heterologous yeast strains. These non‐Gln/Asn repeat Sup35s propagated a novel [PSI+] variant, [PHI+], that appeared de novo 103 times more frequent than [PSI+]. [PHI+] was stably inherited in a non‐Mendelian fashion, but not eliminated upon the inactivation of Hsp104, unlike known [PSI+] elements. In vitro, non‐Gln/Asn repeat domains formed amyloid fibres that were shorter and grew more slowly than did Gln/Asn‐rich prion domains, while [PHI+] aggregates were smaller than [PSI+] aggregates in vivo. Conclusions: These findings suggest the existence of an alternative, Hsp104‐independent pathway to replicate non‐Gln/Asn variant Sup35 prion seeds.