衔接蛋白依赖性降解细胞周期调控因子利用了独特的底物结构。
Adaptor-dependent degradation of a cell-cycle regulator uses a unique substrate architecture.
机构信息
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Amherst, MA 01003, USA.
出版信息
Structure. 2012 Jul 3;20(7):1223-32. doi: 10.1016/j.str.2012.04.019. Epub 2012 Jun 7.
Abstract
In Caulobacter crescentus, the ClpXP protease degrades several crucial cell-cycle regulators, including the phosphodiesterase PdeA. Degradation of PdeA requires the response regulator CpdR and signals a morphological transition in concert with initiation of DNA replication. Here, we report the structure of a Per-Arnt-Sim (PAS) domain of PdeA and show that it is necessary for CpdR-dependent degradation in vivo and in vitro. CpdR acts as an adaptor, tethering the amino-terminal PAS domain to ClpXP and promoting recognition of the weak carboxyl-terminal degron of PdeA, a combination that ensures processive proteolysis. We identify sites on the PAS domain needed for CpdR recognition and find that one subunit of the PdeA dimer can be delivered to ClpXP by its partner. Finally, we show that improper stabilization of PdeA in vivo alters cellular behavior. These results introduce an adaptor/substrate pair for ClpXP and reveal broad diversity in adaptor-mediated proteolysis.
摘要
在新月柄杆菌中，ClpXP 蛋白酶会降解几种关键的细胞周期调节剂，包括磷酸二酯酶 PdeA。PdeA 的降解需要应答调节子 CpdR，并与 DNA 复制的起始协同发出形态转变的信号。在这里，我们报告了 PdeA 的一个 PER-ARNT-SIM（PAS）结构域的结构，并表明它是 CpdR 依赖性在体内和体外降解所必需的。CpdR 作为衔接蛋白，将氨基末端 PAS 结构域与 ClpXP 连接起来，并促进对 PdeA 弱羧基末端降解物的识别，这种组合确保了连续的蛋白水解。我们确定了 PAS 结构域上需要 CpdR 识别的位点，并发现 PdeA 二聚体的一个亚基可以通过其伴侣递送到 ClpXP。最后，我们表明 PdeA 在体内的不当稳定会改变细胞行为。这些结果为 ClpXP 引入了一个衔接子/底物对，并揭示了衔接子介导的蛋白水解的广泛多样性。
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