Department of Biochemistry and Molecular Biology, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA; email:
Annu Rev Biochem. 2018 Jun 20;87:677-696. doi: 10.1146/annurev-biochem-062917-012848. Epub 2018 Apr 12.
Regulated proteolysis is a vital process that affects all living things. Bacteria use energy-dependent AAA+ proteases to power degradation of misfolded and native regulatory proteins. Given that proteolysis is an irreversible event, specificity and selectivity in degrading substrates are key. Specificity is often augmented through the use of adaptors that modify the inherent specificity of the proteolytic machinery. Regulated protein degradation is intricately linked to quality control, cell-cycle progression, and physiological transitions. In this review, we highlight recent work that has shed light on our understanding of regulated proteolysis in bacteria. We discuss the role AAA+ proteases play during balanced growth as well as how these proteases are deployed during changes in growth. We present examples of how protease selectivity can be controlled in increasingly complex ways. Finally, we describe how coupling a core recognition determinant to one or more modifying agents is a general theme for regulated protein degradation.
调控蛋白水解是一个影响所有生物的重要过程。细菌利用依赖能量的 AAA+ 蛋白酶来驱动错误折叠和天然调节蛋白的降解。鉴于蛋白水解是一个不可逆的事件,在降解底物时特异性和选择性是关键。通过使用修饰蛋白酶固有特异性的衔接蛋白,通常可以增强特异性。调控蛋白降解与质量控制、细胞周期进程和生理转变密切相关。在这篇综述中,我们强调了最近的工作,这些工作阐明了我们对细菌中调控蛋白水解的理解。我们讨论了 AAA+ 蛋白酶在平衡生长过程中的作用,以及这些蛋白酶在生长变化时是如何被部署的。我们介绍了蛋白酶选择性可以以越来越复杂的方式被控制的例子。最后,我们描述了如何将核心识别决定因素与一个或多个修饰剂结合起来,这是调控蛋白降解的一个普遍主题。