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A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes

机译:异二聚体复合物,可促进哺乳动物20S蛋白酶体的组装

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The 26S proteasome is a multisubunit protease responsible for regulated proteolysis in eukaryotic cells. It comprises one catalytic 20S proteasome and two axially positioned 19S regulatory complexes. The 20S proteasome is composed of 28 subunits arranged in a cylindrical particle as four heteroheptameric rings, α_(1-7)β_(1-7)_(1-7)α_(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 α-ring formation and keeps the α-rings competent for the subsequent formation of half-proteasomes. Thus, our results identify a mechanism for the correct assembly of 20S proteasomes.
机译:26S蛋白酶体是一种多亚基蛋白酶,负责真核细胞中的蛋白水解。它包含一个催化的20S蛋白酶体和两个轴向定位的19S调节复合物。 20S蛋白酶体由28个亚单位组成,排列成圆柱形颗粒,为四个杂七聚环,即α_(1-7)β_(1-7)_(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,我们报告两个伴侣,称为蛋白酶体组装伴侣1(PAC1)和PAC2,参与哺乳动物20S蛋白酶体的成熟。 PAC1和PAC2作为异二聚体与蛋白酶体前体缔合,并在完成20S蛋白酶体形成后降解。 PAC1或PAC2的过表达会加速前体蛋白酶体的形成,而短时干扰RNA的敲低会削弱它,从而导致20S蛋白酶体的不良成熟。此外,PAC复合物为α环的形成提供了支架,并使α环能够胜任随后的半蛋白酶体的形成。因此,我们的结果确定了正确组装20S蛋白酶体的机制。

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