title: Pba3-Pba4 heterodimer acts as a molecular matchmaker in proteasome α-ring formation.
abstract: Eukaryotic proteasome assembly is assisted by multiple dedicated chaperones. In yeast, formation of the heteroheptameric ring composed of α1-α7 subunits is promoted by the heterodimeric chaperone Pba3-Pba4. Here we reveal that in the absence of this dimeric chaperone, α2 replaces α4 during α-ring assembly, thereby giving rise to a non-productive complex that lacks α4, β1, β5, β6, and β7 subunits and aggregates of α4. Furthermore, our structure-guided mutational data demonstrate that the Pba3-Pba4 heterodimer acts as molecular matchmaker reinforcing the interaction between α4 and α5, which is the crucial step in the α-ring formation.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Laboratory of Protein Metabolism, Department of Integrated Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yashiroda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kaiho
authors.affiliation: Laboratory of Protein Metabolism, Department of Integrated Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamane
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: mizushi@sci.u-hyogo.ac.jp.
authors.forename: Tsunehiro
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Institute for Molecular Science and Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama Myodaiji, Okazaki 444-8787, Japan. Electronic address: kkatonmr@ims.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D004926:Escherichia coli / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C527523:IRC25 protein, S cerevisiae; D018832:Molecular Chaperones; C527522:POC4 protein, S cerevisiae; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Assembly chaperone; Molecular matchmaker; Proteasome; Structure-guided mutagenesis