Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation |
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| Authors: | Eiji Kurimoto Tadashi Satoh Yuri Ito Eri Ishihara Kenta Okamoto Maho Yagi‐Utsumi Keiji Tanaka Koichi Kato |
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| Institution: | 1. Faculty of Pharmacy, Meijo University, Tempaku‐ku, Nagoya, Japan;2. Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho‐ku, Nagoya, Japan;3. JST, PRESTO, Mizuho‐ku, Nagoya, Japan;4. Okazaki Institute for Integrative Bioscience and Institute for Molecular Science, National Institutes of Natural Sciences, Okazaki, Aichi, Japan;5. Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Setagaya‐ku, Tokyo, Japan |
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| 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. |
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| Keywords: | assembly chaperone crystal structure PAC4 proteasome |
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