title: Specificity of class II Hsp40 Sis1 in maintenance of yeast prion [RNQ+].
abstract: Sis1 and Ydj1, functionally distinct heat shock protein (Hsp)40 molecular chaperones of the yeast cytosol, are homologs of Hdj1 and Hdj2 of mammalian cells, respectively. Sis1 is necessary for propagation of the Saccharomyces cerevisiae prion [RNQ(+)]; Ydj1 is not. The ability to function in [RNQ(+)] maintenance has been conserved, because Hdj1 can function to maintain Rnq1 in an aggregated form in place of Sis1, but Hdj2 cannot. An extended glycine-rich region of Sis1, composed of a region rich in phenylalanine residues (G/F) and another rich in methionine residues (G/M), is critical for prion maintenance. Single amino acid alterations in a short stretch of amino acids of the G/F region of Sis1 that are absent in the otherwise highly conserved G/F region of Ydj1 cause defects in prion maintenance. However, there is some functional redundancy within the glycine-rich regions of Sis1, because a deletion of the adjacent glycine/methionine (G/M) region was somewhat defective in propagation of [RNQ(+)] as well. These results are consistent with a model in which the glycine-rich regions of Hsp40s contain specific determinants of function manifested through interaction with Hsp70s.
authors.affiliation: Department of Bacteriology, University of Wisconsin, Madison, 53706, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lopez
authors.forename: Rebecca
authors.initials: R
authors.lastname: Aron
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Craig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; C070320:SIS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C070319:YDJ1 protein, S cerevisiae; D005998:Glycine