FtsH degrades kinetically stable dimers of cyclopropane fatty acid synthase via an internal degron.

FtsH degrades kinetically stable dimers of cyclopropane fatty acid synthase via an internal degron.
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DOI:
10.1111/mmi.15009
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发表时间:
2023-01
影响因子:
3.6
通讯作者:
Sauer, Robert T.
Sauer, Robert T.
中科院分区:
生物学2区
文献类型:
--
作者:
Hari, Sanjay B.;Morehouse, Juhee P.;Baker, Tania A.;Sauer, Robert T.

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靶向蛋白质降解在所有细胞的应激反应中起重要作用。在大肠在大肠杆菌中,膜结合的AAA+ FtsH蛋白酶降解细胞质和膜蛋白。在这里,我们表明,FtsH降解环丙烷脂肪酸(CFA)合酶,其合成诱导后营养剥夺和进入静止期。我们发现,无论是无序的N-末端残基,也不是结构的C-末端残基的动力学稳定的CFA-合酶二聚体所需的FtsH识别和降解。融合蛋白的实验支持一种模型,其中内部降解决定子介导FtsH识别作为展开和蛋白水解的前奏。这些发现阐明了CFA合酶生命周期中的终末步骤,并为FtsH功能提供了新的见解。细胞蛋白质组处于恒定的流动状态,因为环境的变化需要快速的功能反应,通常通过涉及蛋白质降解的机制。FtsH是一种膜结合AAA+蛋白酶,降解环丙烷脂肪酸合酶,该酶在进入固定相时瞬时上调。有趣的是,FtsH似乎利用CFA合酶的内部序列进行底物识别,而不是在N-或C-末端的降解决定子。
Targeted protein degradation plays important roles in stress responses in all cells. In E. coli, the membrane-bound AAA+ FtsH protease degrades cytoplasmic and membrane proteins. Here, we demonstrate that FtsH degrades cyclopropane fatty acid (CFA) synthase, whose synthesis is induced upon nutrient deprivation and entry into stationary phase. We find that neither the disordered N-terminal residues nor the structured C-terminal residues of the kinetically stable CFA-synthase dimer are required for FtsH recognition and degradation. Experiments with fusion proteins support a model in which an internal degron mediates FtsH recognition as a prelude to unfolding and proteolysis. These findings elucidate the terminal step in the life cycle of CFA synthase and provide new insight into FtsH function. The cellular proteome is in a constant state of flux, as changes in the environment necessitate rapid functional responses, often via mechanisms involving protein degradation. FtsH, a membrane-bound AAA+ protease, degrades cyclopropane fatty acid synthase, an enzyme that is transiently upregulated upon entrance into stationary phase. Interestingly, FtsH appears to utilize an internal sequence of CFA synthase for substrate recognition rather than degrons at either the N- or C-terminus.
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