Assembly Pathway of the Mammalian Proteasome Base Subcomplex Is Mediated by Multiple Specific Chaperones
Assembly Pathway of the Mammalian Proteasome Base Subcomplex Is Mediated by Multiple Specific Chaperones
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DOI：
10.1016/j.cell.2009.05.008
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发表时间：
2009-05-29
期刊：
影响因子：
64.5
通讯作者：
Murata, Shigeo
中科院分区：
文献类型：
--
作者：
Kaneko, Takeumi;Hamazaki, Jun;Murata, Shigeo
26 S蛋白酶体是一种降解真核细胞中泛素化蛋白的酶复合物。它由20 S核心颗粒（CP）和19 S调节颗粒（RP）组成。后者进一步分为盖和基地子复合物。虽然CP组装的机制已经得到了很好的研究，但RP的组装机制却知之甚少。在这里，我们表明，哺乳动物的碱基亚复合物的形成涉及三个不同的模块，其中特定的ATP酶亚基对与不同的伴侣蛋白p28，S5 b，或p27。碱基形成的过程始于p28-Rpt 3-Rpt 6-Rpn 14复合物与S5 b-Rpt 1-Rpt 2-Rpn 1复合物的结合，随后是p27-Rpt 5-Rpt 4复合物和Rpn 2的掺入，其中p28、S5 b和p27调节模块之间的结合。这些分子伴侣在26 S蛋白酶体形成完成之前解离。我们的研究结果表明，基地组装是由多个蛋白酶体专用的分子伴侣，如CP组装。
The 26S proteasome is an enzymatic complex that degrades ubiquitinated proteins in eukaryotic cells. It is composed of the 20S core particle (CP) and the 19S regulatory particle (RP). The latter is further divided into the lid and base subcomplexes. While the mechanism involved in the assembly of the CP is well investigated, that of the RP is poorly understood. Here, we show that the formation of the mammalian base subcomplex involves three distinct modules, where specific pairs of ATPase subunits are associated with the distinct chaperones p28, S5b, or p27. The process of base formation starts from association of the p28-Rpt3-Rpt6-Rpn14 complex with the S5b-Rpt1-Rpt2-Rpn1 complex, followed by incorporation of the p27-Rpt5-Rpt4 complex and Rpn2, where p28, S5b, and p27 regulate the associations between the modules. These chaperones dissociate before completion of 26S proteasome formation. Our results demonstrate that base assembly is facilitated by multiple proteasome-dedicated chaperones, like CP assembly.