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Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation
Author(s) -
Kurimoto Eiji,
Satoh Tadashi,
Ito Yuri,
Ishihara Eri,
Okamoto Kenta,
YagiUtsumi Maho,
Tanaka Keiji,
Kato Koichi
Publication year - 2017
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3153
Subject(s) - proteasome , chaperone (clinical) , crystal structure , microbiology and biotechnology , chemistry , hydrolase , biophysics , co chaperone , crystallography , hsp90 , biochemistry , biology , enzyme , medicine , heat shock protein , gene , pathology
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.