[PHI+], a novel Sup35-prion variant propagated with non-Gln/Asn oligopeptide repeats in the absence of the chaperone protein Hsp104
✍ Scribed by Colin G. Crist; Toru Nakayashiki; Hiroshi Kurahashi; Yoshikazu Nakamura
- Book ID
- 104460500
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 447 KB
- Volume
- 8
- Category
- Article
- ISSN
- 1356-9597
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✦ Synopsis
Abstract
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 10^3^ 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.