NR AOFM
AU Crist,C.G.; Nakayashiki,T.; Kurahashi,H.; Nakamura,Y.
TI [PHI+], a novel Sup35-prion variant propagated with non-Gln/Asn oligopeptide repeats in the absence of the chaperone protein Hsp104
QU Genes to Cells : devoted to molecular & cellular mechanisms 2003 Jul; 8(7): 603-18
PT journal article
AB 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.
MH Amino Acid Sequence; Asparagine/*chemistry; Base Sequence; DNA Primers; Glycine/*chemistry; Heat-Shock Proteins/*metabolism; Molecular Sequence Data; Prions/chemistry/*genetics/metabolism; Repetitive Sequences, Amino Acid; Saccharomyces cerevisiae Proteins/chemistry/*genetics/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.
AD Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
SP englisch
PO England