ATP hydrolysis-dependent disassembly of the 26S proteasome is part of the catalytic cycle (Retracted article. See vol. 173, pg. 804, 2018)
ATP hydrolysis-dependent disassembly of the 26S proteasome is part of the catalytic cycle (Retracted article. See vol. 173, pg. 804, 2018)
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DOI：
10.1016/j.cell.2005.03.028
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发表时间：
2005-05-20
期刊：
影响因子：
64.5
通讯作者：
Skowyra, D
中科院分区：
文献类型：
--
作者：
Babbitt, SE;Kiss, A;Skowyra, D
ATP水解是26 S蛋白酶体降解多泛素化蛋白质所必需的，但被认为在催化循环期间对蛋白酶体的稳定性没有作用。与此相反，我们报告说，ATP水解触发快速解离的19 S调节颗粒从免疫纯化的26 S复合物的方式与释放大量的蛋白酶体相互作用蛋白。引人注目的是，这种机制导致19 S定量分解成亚复合物和游离的多聚泛素结合亚基Rpn 10。生化重建纯化的Sic 1，原型基板的Cdc 34/ SCF泛素连接酶，表明底物降解是必不可少的触发ATP水解依赖性的解离和拆卸的19 S，这种机制导致释放的降解产物。这是第一次证明19 S调节颗粒与26 S蛋白酶体的受控解离是蛋白质降解机制的一部分。
ATP hydrolysis is required for degradation of poly-ubiquitinated proteins by the 26S proteasome but is thought to play no role in proteasomal stability during the catalytic cycle. In contrast to this view, we report that ATP hydrolysis triggers rapid dissociation of the 19S regulatory particles from immunopurified 26S complexes in a manner coincident with release of the bulk of proteasome-interacting proteins. Strikingly, this mechanism leads to quantitative disassembly of the 19S into subcomplexes and free Rpn10, the polyubiquitin binding subunit. Biochemical reconstitution with purified Sic1, a prototype substrate of the Cdc34/ SCF ubiquitin ligase, suggests that substrate degradation is essential for triggering the ATP hydrolysis-dependent dissociation and disassembly of the 19S and that this mechanism leads to release of degradation products. This is the first demonstration that a controlled dissociation of the 19S regulatory particles from the 26S proteasome is part of the mechanism of protein degradation.