Bittner Lisa-Marie, Arends Jan, Narberhaus Franz
Microbial Biology, Ruhr University Bochum, Universitätsstr. 150, NDEF 06/783, D-44801 Bochum.
Biol Chem. 2017 May 1;398(5-6):625-635. doi: 10.1515/hsz-2016-0302.
Cellular proteomes are dynamic and adjusted to permanently changing conditions by ATP-fueled proteolytic machineries. Among the five AAA+ proteases in Escherichia coli FtsH is the only essential and membrane-anchored metalloprotease. FtsH is a homohexamer that uses its ATPase domain to unfold and translocate substrates that are subsequently degraded without the need of ATP in the proteolytic chamber of the protease domain. FtsH eliminates misfolded proteins in the context of general quality control and properly folded proteins for regulatory reasons. Recent trapping approaches have revealed a number of novel FtsH substrates. This review summarizes the substrate diversity of FtsH and presents details on the surprisingly diverse recognition principles of three well-characterized substrates: LpxC, the key enzyme of lipopolysaccharide biosynthesis; RpoH, the alternative heat-shock sigma factor and YfgM, a bifunctional membrane protein implicated in periplasmic chaperone functions and cytoplasmic stress adaptation.
细胞蛋白质组是动态的，并通过由ATP驱动的蛋白水解机制来适应不断变化的条件。在大肠杆菌的五种AAA+蛋白酶中，FtsH是唯一必需的且锚定在膜上的金属蛋白酶。FtsH是一种同六聚体，它利用其ATP酶结构域来展开和转运底物，这些底物随后在蛋白酶结构域的蛋白水解腔内无需ATP即可被降解。FtsH在一般质量控制的背景下消除错误折叠的蛋白质，并出于调节原因消除正确折叠的蛋白质。最近的捕获方法揭示了许多新的FtsH底物。这篇综述总结了FtsH的底物多样性，并详细介绍了三种特征明确的底物令人惊讶的多样识别原则：LpxC，脂多糖生物合成中的关键酶；RpoH，替代热休克σ因子；以及YfgM，一种双功能膜蛋白，参与周质伴侣功能和细胞质应激适应。
