Gur Eyal, Ottofueling Ralf, Dougan David A
Life Sciences Department, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel,
Subcell Biochem. 2013;66:3-33. doi: 10.1007/978-94-007-5940-4_1.
Bacteria are frequently exposed to changes in environmental conditions, such as fluctuations in temperature, pH or the availability of nutrients. These assaults can be detrimental to cell as they often result in a proteotoxic stress, which can cause the accumulation of unfolded proteins. In order to restore a productive folding environment in the cell, bacteria have evolved a network of proteins, known as the protein quality control (PQC) network, which is composed of both chaperones and AAA+ proteases. These AAA+ proteases form a major part of this PQC network, as they are responsible for the removal of unwanted and damaged proteins. They also play an important role in the turnover of specific regulatory or tagged proteins. In this review, we describe the general features of an AAA+ protease, and using two of the best-characterised AAA+ proteases in Escherichia coli (ClpAP and ClpXP) as a model for all AAA+ proteases, we provide a detailed mechanistic description of how these machines work. Specifically, the review examines the physiological role of these machines, as well as the substrates and the adaptor proteins that modulate their substrate specificity.
细菌经常暴露于环境条件的变化中，例如温度、pH值或营养物质可用性的波动。这些冲击可能对细胞有害，因为它们常常导致蛋白毒性应激，进而可能导致未折叠蛋白的积累。为了在细胞中恢复一个有利于蛋白质折叠的环境，细菌进化出了一个蛋白质网络，即蛋白质质量控制（PQC）网络，它由伴侣蛋白和AAA+蛋白酶组成。这些AAA+蛋白酶构成了这个PQC网络的主要部分，因为它们负责清除不需要的和受损的蛋白质。它们在特定调节蛋白或标记蛋白的周转中也起着重要作用。在这篇综述中，我们描述了AAA+蛋白酶的一般特征，并以大肠杆菌中两个特征最明确的AAA+蛋白酶（ClpAP和ClpXP）作为所有AAA+蛋白酶的模型，详细阐述了这些机器的工作机制。具体而言，这篇综述探讨了这些机器的生理作用，以及调节其底物特异性的底物和衔接蛋白。
