title: N-terminal α7 deletion of the proteasome 20S core particle substitutes for yeast PI31 function.
abstract: The proteasome core particle (CP) is a conserved protease complex that is formed by the stacking of two outer α-rings and two inner β-rings. The α-ring is a heteroheptameric ring of subunits α1 to α7 and acts as a gate that restricts entry of substrate proteins into the catalytic cavity formed by the two abutting β-rings. The 31-kDa proteasome inhibitor (PI31) was originally identified as a protein that binds to the CP and inhibits CP activity in vitro, but accumulating evidence indicates that PI31 is required for physiological proteasome activity. To clarify the in vivo role of PI31, we examined the Saccharomyces cerevisiae PI31 ortholog Fub1. Fub1 was essential in a situation where the CP assembly chaperone Pba4 was deleted. The lethality of Δfub1 Δpba4 was suppressed by deletion of the N terminus of α7 (α7ΔN), which led to the partial activation of the CP. However, deletion of the N terminus of α3, which activates the CP more efficiently than α7ΔN by gate opening, did not suppress Δfub1 Δpba4 lethality. These results suggest that the α7 N terminus has a role in CP activation different from that of the α3 N terminus and that the role of Fub1 antagonizes a specific function of the α7 N terminus.
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yashiroda
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Toda
authors.affiliation: Picobiology Institute, Department of Life Science, Graduate School of Life Science, University of Hyogo, Ako-gun, Hyogo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Otsu
authors.affiliation: Picobiology Institute, Department of Life Science, Graduate School of Life Science, University of Hyogo, Ako-gun, Hyogo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Picobiology Institute, Department of Life Science, Graduate School of Life Science, University of Hyogo, Ako-gun, Hyogo, Japan.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan smurata@mol.f.u-tokyo.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
mesh_terms: D000483:Alleles; D018360:Crystallography, X-Ray; D017353:Gene Deletion; D005816:Genetic Complementation Test; D005990:Glycerol / Q000737:chemistry; D006579:Heterozygote; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C573493:Fub1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex; D005990:Glycerol