title: A systematic evaluation of the function of the protein-remodeling factor Hsp104 in [PSI+] prion propagation in S. cerevisiae by comprehensive chromosomal mutations.
abstract: The yeast prion [PSI(+)] represents an aggregated state of the translational release factor Sup35 (eRF3) and deprives termination complexes of functional Sup35, resulting in nonsense codon suppression. Protein-remodeling factor Hsp104 is involved in thermotolerance and [PSI(+)] propagation, however the structure-and-function relationship of Hsp104 for [PSI(+)] remains unclear. In this study, we engineered 58 chromosomal hsp104 mutants that affect residues considered structurally or functionally relevant to Hsp104 remodeling activity, yet most remain to be examined for their significance to [PSI(+)] in the same genetic background. Many of these hsp104 mutants were affected both in thermotolerance and [PSI(+)] propagation. However, nine mutants were impaired exclusively for [PSI(+)], while two mutants were impaired exclusively for thermotolerance. Mutations exclusively affecting [PSI(+)] are clustered around the lateral channel of the Hsp104 hexamer. These findings suggest that Hsp104 possesses shared as well as distinct remodeling activities for stress-induced protein aggregates and [PSI(+)] prion aggregates and that the lateral channel plays a role specific to [PSI(+)] prion propagation.
authors.affiliation: Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Takahashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics / Q000378:metabolism*; D018389:Codon, Nonsense / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000235:genetics; D006358:Hot Temperature; D009154:Mutation; D010454:Peptide Termination Factors; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018389:Codon, Nonsense; D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae