A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes
A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes
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DOI：
10.1038/nature04106
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发表时间：
2005-10-27
期刊：
影响因子：
64.8
通讯作者：
Murata, S
中科院分区：
文献类型：
--
作者：
Hirano, Y;Hendil, KB;Murata, S
26 S蛋白酶体是一种多亚基蛋白酶，负责真核细胞中的调节蛋白水解（1，2）。它包含一个催化20 S蛋白酶体和两个轴向定位的19 S调节复合物（3）。20 S蛋白酶体由28个亚基组成，排列在一个圆柱形颗粒中，形成四个异七聚体环，α（1 - 7）β（1 - 7）β（1-7）α（1-7）（参考文献4，5），但负责组装这种复杂结构的机制仍然难以捉摸。在这里，我们报告了两个分子伴侣，蛋白酶体组装分子伴侣1（PAC 1）和PAC 2，参与了哺乳动物20 S蛋白酶体的成熟。PAC 1和PAC 2作为异二聚体与蛋白酶体前体结合，并在20 S蛋白酶体形成完成后降解。PAC 1或PAC 2的过表达加速前体蛋白酶体的形成，而短干扰RNA的敲低则会损害前体蛋白酶体的形成，导致20 S蛋白酶体的成熟不良。此外，PAC复合物为α-环形成提供了支架，并保持α-环能够随后形成半蛋白酶体。因此，我们的研究结果确定了20 S蛋白酶体正确组装的机制。
The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells(1,2). It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes(3). The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, alpha(1-7)beta(1-7)beta(1-7)alpha(1-7) ( refs 4, 5), but the mechanism responsible for the assembly of such a complex structure remains elusive. Here we report two chaperones, designated proteasome assembling chaperone-1 (PAC1) and PAC2, that are involved in the maturation of mammalian 20S proteasomes. PAC1 and PAC2 associate as heterodimers with proteasome precursors and are degraded after formation of the 20S proteasome is completed. Overexpression of PAC1 or PAC2 accelerates the formation of precursor proteasomes, whereas knockdown by short interfering RNA impairs it, resulting in poor maturation of 20S proteasomes. Furthermore, the PAC complex provides a scaffold for alpha-ring formation and keeps the alpha-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.