An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle.
An Adaptor Hierarchy Regulates Proteolysis during a Bacterial Cell Cycle.
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DOI：
10.1016/j.cell.2015.09.030
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发表时间：
2015-10-08
期刊：
影响因子：
64.5
通讯作者：
Chien P
中科院分区：
文献类型：
--
作者：
Joshi KK;Bergé M;Radhakrishnan SK;Viollier PH;Chien P
受调控的蛋白质降解是必不可少的。ClpXP蛋白酶对关键蛋白质的定时破坏推动了新月弯杆菌的细胞周期进展。虽然ClpXP单独是活性的，但令人费解的是，细胞周期依赖的蛋白质分解需要额外的因素。在这里，我们证明了这些因素构成了一个适配器层次结构，其中根据适配器组装的程度破坏不同的底物。该层次建立在适配器CpdR对ClpXP的引发的基础上，该适配器CpdR促进一类底物的降解，并招募适配器RCDA降解第二类底物。添加POPA适配器促进了第三类底物的破坏，同时抑制了第二类底物的降解。我们解剖RCDA以生成定制的适配器，识别识别RCDA所需的关键底物元素，并发现额外的细胞周期依赖的ClpXP底物。我们的工作揭示了在细菌细胞周期进展过程中，分层适配器和启动的蛋白酶如何协调受调控的蛋白分解。
Regulated protein degradation is essential. The timed destruction of crucial proteins by the ClpXP protease drives cell-cycle progression in the bacterium Caulobacter crescentus. Although ClpXP is active alone, additional factors are inexplicably required for cell-cycle dependent proteolysis. Here, we show that these factors constitute an adaptor hierarchy where different substrates are destroyed based on the degree of adaptor assembly. The hierarchy builds upon priming of ClpXP by the adaptor CpdR, which promotes degradation of one class of substrates and also recruits the adaptor RcdA to degrade a second class of substrates. Adding the PopA adaptor promotes destruction of a third class of substrates, while inhibiting degradation of the second class. We dissect RcdA to generate bespoke adaptors, identifying critical substrate elements needed for RcdA recognition and uncovering additional cell-cycle dependent ClpXP substrates. Our work reveals how hierarchical adaptors and primed proteases orchestrate regulated proteolysis during bacterial cell-cycle progression.