Reconfiguration of the proteasome during chaperone-mediated assembly.
Reconfiguration of the proteasome during chaperone-mediated assembly.
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蛋白酶体ATP酶环由Rpt 1-Rpt 6组成，与成熟蛋白酶体中蛋白酶体核心颗粒（CP）的七聚体α环相连，Rpt C端尾部插入α环的口袋中。Rpt环组装由四个分子伴侣介导，每个分子伴侣结合不同的Rpt亚基。我们报告，该蛋白酶体，其中包括RPT环的基础组件，形成了高亲和力的复合物与CP。该复合物受到分子伴侣Hsm 3、Nas 6和Rpn 14的主动解离。分子伴侣介导的解离被废除的nonhydrolyzable ATP类似物，表明分子伴侣的行动是耦合到核苷酸水解的RPT环。出乎意料的是，合成的Rpt尾肽以较差的特异性结合α口袋，除了Rpt 6，其独特地结合α2/α3口袋。虽然Rpt 6尾在成熟蛋白酶体中的α口袋中不可见，但它插入碱基-CP复合物中的α2/α3口袋中，对复合物的形成很重要。因此，Rpt-CP接口重新配置时，盖复合物加入新生的蛋白酶体，形成成熟的全酶。
The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt C-terminal tails inserting into pockets of the α ring. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit. We report that the base subassembly of the proteasome, which includes the Rpt ring, forms a high affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6, and Rpn14. Chaperone-mediated dissociation was abrogated by a nonhydrolyzable ATP analog, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound α pockets with poor specificity, except for Rpt6, which uniquely bound the α2/α3 pocket. Although the Rpt6 tail is not visualized within an α pocket in mature proteasomes, it inserts into the α2/α3 pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.
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影响因子：
16
作者：
Tomko RJ Jr;Funakoshi M;Schneider K;Wang J;Hochstrasser M
通讯作者：
Hochstrasser M
影响因子：
64.8
作者：
Lander, Gabriel C.;Estrin, Eric;Matyskiela, Mary E.;Bashore, Charlene;Nogales, Eva;Martin, Andreas
通讯作者：
Martin, Andreas
影响因子：
16
作者：
Smith, DM;Kafri, G;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
16.8
作者：
Kusmierczyk, Andrew R.;Kunjappu, Mary J.;Hochstrasser, Mark
通讯作者：
Hochstrasser, Mark
影响因子：
16.8
作者：
Tian, Geng;Park, Soyeon;Finley, Daniel
通讯作者：
Finley, Daniel