Satoh Tadashi, Saeki Yasushi, Hiromoto Takeshi, Wang Ying-Hui, Uekusa Yoshinori, Yagi Hirokazu, Yoshihara Hidehito, Yagi-Utsumi Maho, Mizushima Tsunehiro, Tanaka Keiji, Kato Koichi
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; JST, PRESTO, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Structure. 2014 May 6;22(5):731-43. doi: 10.1016/j.str.2014.02.014. Epub 2014 Mar 27.
Proteasome formation does not occur due to spontaneous self-organization but results from a highly ordered process assisted by several assembly chaperones. The assembly of the proteasome ATPase subunits is assisted by four client-specific chaperones, of which three have been structurally resolved. Here, we provide the structural basis for the working mechanisms of the last, hereto structurally uncharacterized assembly chaperone, Nas2. We revealed that Nas2 binds to the Rpt5 subunit in a bivalent mode: the N-terminal helical domain of Nas2 masks the Rpt1-interacting surface of Rpt5, whereas its C-terminal PDZ domain caps the C-terminal proteasome-activating motif. Thus, Nas2 operates as a proteasome activation blocker, offering a checkpoint during the formation of the 19S ATPase prior to its docking onto the proteolytic 20S core particle.
蛋白酶体的形成并非由于自发的自我组织，而是源于一个由几种组装伴侣辅助的高度有序的过程。蛋白酶体ATP酶亚基的组装由四种客户特异性伴侣辅助，其中三种的结构已得到解析。在这里，我们提供了最后一种在结构上尚未表征的组装伴侣Nas2工作机制的结构基础。我们发现Nas2以二价模式与Rpt5亚基结合：Nas2的N端螺旋结构域掩盖了Rpt5与Rpt1相互作用的表面，而其C端PDZ结构域覆盖了C端蛋白酶体激活基序。因此，Nas2作为蛋白酶体激活阻滞剂发挥作用，在19S ATP酶对接至蛋白水解性20S核心颗粒之前的形成过程中提供一个检查点。
