Identification and structural-functional analysis of shuttle-type proteasome activator exhibiting molecular chaperone activity

真核生物20 S蛋白酶体的组装不是自发的自组织，而是一个有序的过程，涉及几个组装分子伴侣，而古细菌20 S蛋白酶体的组装涉及自发的自组装。最近的基因组分析确定了组装分子伴侣PbaA和PbaB的古细菌同源物。然而，目前还不清楚这种组装伴侣样蛋白在古细菌中蛋白酶体亚基的组装中如何发挥不可或缺的作用。这项研究表明，PbaB实际上是一种蛋白酶体激活剂。此外，我们的综合生化和生物物理方法，包括X-射线晶体学，电子显微镜，核磁共振光谱，和小角中子散射之间形成的PbaB同源四聚体和20 S蛋白酶体的活性复合物的分子作用提供了机制线索。

Assembly of the eukaryotic 20S proteasome is not spontaneous self-organization but an ordered process involving several assembly chaperones, whereas that of the archaeal 20S proteasome involves spontaneous self-assembly. Recent genomic analysis identified archaeal homologs of the assembly chaperones, PbaA and PbaB. However, it remains unclear how such assembly chaperone-like proteins play an indispensable role in assembly of the proteasome subunit in archaea. This study revealed that PbaB actually functions as a proteasome activator. Furthermore, our integrative biochemical and biophysical approach including X-ray crystallography, electron microscopy, NMR spectroscopy, and small-angle neutron scattering provided mechanistic clues to the molecular action of the active complex formed between the PbaB homotetramer and 20S proteasome.