Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation

Kurimoto, EijiMeijo Univ, Fac Pharm, Tempaku Ku, 150 Yagotoyama, Nagoya, Aichi 4688503, Japan. (author)

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-angstrom 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 4-5 subunits. This will provide insights into human proteasome-assembling chaperones as potential anticancer drug targets.

Satoh, TadashiNagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan.;JST, PRESTO, Mizuho Ku, Nagoya, Aichi 4678603, Japan. (author)
Ito, YuriMeijo Univ, Fac Pharm, Tempaku Ku, 150 Yagotoyama, Nagoya, Aichi 4688503, Japan. (author)
Ishihara, EriMeijo Univ, Fac Pharm, Tempaku Ku, 150 Yagotoyama, Nagoya, Aichi 4688503, Japan. (author)
Okamoto, KentaUppsala universitet,Molekylär biofysik,Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan(Swepub:uu)kenok266 (author)
Yagi-Utsumi, MahoNagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan.;Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan.;Natl Inst Nat Sci, Inst Mol Sci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan. (author)
Tanaka, KeijiTokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 1568506, Japan. (author)
Kato, KoichiNagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan.;Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan.;Natl Inst Nat Sci, Inst Mol Sci, 5-1 Higashiyama, Okazaki, Aichi 4448787, Japan. (author)
Meijo Univ, Fac Pharm, Tempaku Ku, 150 Yagotoyama, Nagoya, Aichi 4688503, Japan.Nagoya City Univ, Grad Sch Pharmaceut Sci, Mizuho Ku, Nagoya, Aichi 4678603, Japan.;JST, PRESTO, Mizuho Ku, Nagoya, Aichi 4678603, Japan. (creator_code:org_t)

By the author/editor: Kurimoto, Eiji; Satoh, Tadashi; Ito, Yuri; Ishihara, Eri; Okamoto, Kenta; Yagi-Utsumi, Mah ...; show more...; Tanaka, Keiji; Kato, Koichi; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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