Structural Basis for Proteasome Formation Controlled by an Assembly Chaperone Nas2
Structural Basis for Proteasome Formation Controlled by an Assembly Chaperone Nas2
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DOI：
10.1016/j.str.2014.02.014
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发表时间：
2014-05-06
期刊：
影响因子：
5.7
通讯作者：
Kato, Koichi
中科院分区：
文献类型：
--
作者：
Satoh, Tadashi;Saeki, Yasushi;Kato, Koichi
蛋白酶体的形成不是由于自发的自组织，而是在几个组装伴侣的协助下一个高度有序的过程的结果。蛋白酶体ATPase亚单位的组装由四个客户特定的伴侣协助，其中三个已经在结构上得到解决。在这里，我们为最后一个结构上尚未确定的组装伴侣--Nas2的工作机制提供了结构基础。我们揭示了Nas2以二价方式与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端的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，在19S ATPase与蛋白水解性20S核心颗粒对接之前的形成过程中提供了一个检查点。
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.