Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation
Crystal structure of human proteasome assembly chaperone PAC4 involved in proteasome formation
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参与蛋白酶体形成的人蛋白酶体组装伴侣PAC4的晶体结构
DOI：
10.1002/pro.3153
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
and Koichi Kato
中科院分区：
文献类型：
--
作者：
Eiji Kurimoro;Tadashi Satoh;Yuri Ito;Eri Ishihara;Kenta Okamoto;Maho Yagi-Utsumi;Keiji Tanaka;and Koichi Kato
26 S蛋白酶体是一种大的蛋白质复合物，负责真核细胞中泛素化蛋白的降解。真核生物蛋白酶体的形成是一个高度有序的过程，是由几个组装分子伴侣辅助的。其催化20 S核心颗粒的组装取决于至少五种蛋白酶体特异性伴侣，即，蛋白酶体组装伴侣蛋白1-4（PAC 1 -4）和蛋白酶体成熟蛋白（POMP）。酵母组装分子伴侣的直向同源物已经在结构上表征，而大多数哺乳动物组装分子伴侣没有。在本研究中，我们以1.90 - 100的分辨率确定了人类PAC 4的晶体结构。我们的晶体学数据确定了一个疏水表面，被带电残基包围。疏水表面与其结合伴侣PAC 3的疏水表面互补。表面还显示出与蛋白酶体α4-5亚基的电荷互补性。这将为人类蛋白酶体组装分子伴侣作为潜在的抗癌药物靶标提供见解。
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.