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通过调控蛋白质降解来控制蛋白质功能:生物技术与生物医学应用

Control of protein function through regulated protein degradation: biotechnological and biomedical applications.

作者信息

Nagpal Jyotsna, Tan Ju Lin, Truscott Kaye N, Heras Begoña, Dougan David A

机构信息

Department of Biochemistry, La Trobe Institute for Molecular Science LIMS, La Trobe University, Melbourne, Vic., Australia.

出版信息

J Mol Microbiol Biotechnol. 2013;23(4-5):335-44. doi: 10.1159/000352043. Epub 2013 Aug 5.

Abstract

Targeted protein degradation is crucial for the correct function and maintenance of a cell. In bacteria, this process is largely performed by a handful of ATP-dependent machines, which generally consist of two components - an unfoldase and a peptidase. In some cases, however, substrate recognition by the protease may be regulated by specialized delivery factors (known as adaptor proteins). Our detailed understanding of how these machines are regulated to prevent uncontrolled degradation within a cell has permitted the identification of novel antimicrobials that dysregulate these machines, as well as the development of tunable degradation systems that have applications in biotechnology. Here, we focus on the physiological role of the ClpP peptidase in bacteria, its role as a novel antibiotic target and the use of protein degradation as a biotechnological approach to artificially control the expression levels of a protein of interest.

摘要

靶向蛋白质降解对于细胞的正确功能和维持至关重要。在细菌中,这一过程主要由少数几种依赖ATP的机制来执行,这些机制通常由两个部分组成——一个解折叠酶和一个肽酶。然而,在某些情况下,蛋白酶对底物的识别可能受专门的递送因子(称为衔接蛋白)调控。我们对这些机制如何被调节以防止细胞内不受控制的降解有了详细了解,这使得我们能够鉴定出失调这些机制的新型抗菌药物,以及开发出在生物技术中有应用的可调降解系统。在这里,我们重点关注ClpP肽酶在细菌中的生理作用、其作为新型抗生素靶点的作用以及将蛋白质降解作为一种生物技术方法来人工控制目标蛋白质表达水平的应用。

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