title: Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation.
abstract: The 26S proteasome is a large protein complex, responsible for degradation of ubiquinated proteins in eukaryotic cells. Eukaryotic proteasome formation is a highly ordered process that is assisted by several assembly chaperones. The assembly of its catalytic 20S core particle depends on at least five proteasome-specific chaperones, i.e., proteasome-assembling chaperons 1-4 (PAC1-4) and proteasome maturation protein (POMP). The orthologues of yeast assembly chaperones have been structurally characterized, whereas most mammalian assembly chaperones are not. In the present study, we determined a crystal structure of human PAC4 at 1.90-Å resolution. Our crystallographic data identify a hydrophobic surface that is surrounded by charged residues. The hydrophobic surface is complementary to that of its binding partner, PAC3. The surface also exhibits charge complementarity with the proteasomal α4-5 subunits. This will provide insights into human proteasome-assembling chaperones as potential anticancer drug targets.
authors.affiliation: Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kurimoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, 467-8603, Japan.|JST, PRESTO, Mizuho-ku, Nagoya, 467-8603, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ishihara
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, 467-8603, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Myodaiji, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Yagi-Utsumi
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 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, Mizuho-ku, Nagoya, 467-8603, Japan.|Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Myodaiji, Okazaki, Aichi, 444-8787, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D000072417:Protein Domains; D013329:Structure-Activity Relationship
chemical_list: D018832:Molecular Chaperones; D046988:Proteasome Endopeptidase Complex
keywords: PAC4; assembly chaperone; crystal structure; proteasome