Assembly checkpoint of the proteasome regulatory particle is activated by coordinated actions of proteasomal ATPase chaperones.
Assembly checkpoint of the proteasome regulatory particle is activated by coordinated actions of proteasomal ATPase chaperones.
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DOI：
10.1016/j.celrep.2022.110918
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发表时间：
2022-06-07
期刊：
影响因子：
8.8
通讯作者：
Park, Soyeon
中科院分区：
文献类型：
--
作者：
Nahar, Asrafun;Sokolova, Vladyslava;Sekaran, Suganya;Orth, James D.;Park, Soyeon
蛋白酶体全酶通过降解大多数蛋白质来调节细胞蛋白质组。在其19个亚基调节颗粒(RP)中，异六聚体ATPase通过将蛋白质底物注入核心多肽酶而使蛋白质降解。RP组装利用“检查点”，在那里多个专门的伴侣结合到特定的ATPase亚基上，并控制其他亚基的添加。在这里，我们发现RP组装检查点依赖于伴侣的两个共同功能。单独的伴侣可以区分一个RP，在这个RP中，他们的同源ATPase持续处于ATP结合状态。然后，伴侣共同调节ATPase的活性，以促进RP亚基重排，从而在所产生的蛋白酶体全酶中切换到活跃的底物处理状态。因此，伴侣蛋白可以感知ATP的结合和水解，作为RP复合体质量的读数，以产生功能上的蛋白酶体全酶。我们的发现为在已知蛋白酶体ATPase伴侣蛋白去调控的情况下潜在地利用组装检查点提供了基础。Nahar等人。报告称，细胞通过利用组装检查点来构建功能性蛋白酶体，该检查点由多个专用伴侣的共同特征激活；它们可以区分蛋白酶体ATPase的核苷酸状态，并帮助促进适当的亚基重排，以确保蛋白酶体有效地降解蛋白质。
The proteasome holoenzyme regulates the cellular proteome via degrading most proteins. In its 19-subunit regulatory particle (RP), a heterohexameric ATPase enables protein degradation by injecting protein substrates into the core peptidase. RP assembly utilizes “checkpoints,” where multiple dedicated chaperones bind to specific ATPase subunits and control the addition of other subunits. Here, we find that the RP assembly checkpoint relies on two common features of the chaperones. Individual chaperones can distinguish an RP, in which their cognate ATPase persists in the ATP-bound state. Chaperones then together modulate ATPase activity to facilitate RP subunit rearrangements for switching to an active, substrate-processing state in the resulting proteasome holoenzyme. Thus, chaperones may sense ATP binding and hydrolysis as a readout for the quality of the RP complex to generate a functional proteasome holoenzyme. Our findings provide a basis to potentially exploit the assembly checkpoints in situations with known deregulation of proteasomal ATPase chaperones. Nahar et al. report that cells build functional proteasomes by utilizing an assembly checkpoint, which is activated by a common feature of multiple dedicated chaperones; they can distinguish the nucleotide state of proteasomal ATPases and help facilitate proper subunit rearrangement to ensure efficient protein degradation by the proteasome.
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影响因子：
7.2
作者：
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通讯作者：
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影响因子：
4.6
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DOI：
10.1038/80992
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2000-11-01
期刊：
NATURE STRUCTURAL BIOLOGY
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作者：
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通讯作者：
VARSHAVSKY, A
DOI：
10.1073/pnas.1805353115
发表时间：
2018-12-26
影响因子：
11.1
作者：
Fu, Xinyi;Sokolova, Vladyslava;Park, Soyeon
通讯作者：
Park, Soyeon