Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.
Genetic Code Expansion: A Powerful Tool for Understanding the Physiological Consequences of Oxidative Stress Protein Modifications.
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DOI：
10.1155/2018/7607463
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发表时间：
2018
影响因子：
--
通讯作者：
Mehl RA
中科院分区：
文献类型：
--
作者：
Porter JJ;Mehl RA
在氧化应激条件下以及基础条件下，细胞内存在由蛋白质氧化引起的翻译后修饰（Ox-PTM）。过去，这些修饰被认为是一般的蛋白质损伤，但越来越清楚的是，Ox-PTM可以具有特定的生理作用。区分这两种情况是一项艰巨的任务，因为多个Ox-PTM同时发生在同一蛋白质上，使分析复杂化。遗传密码扩展（GCE）已成为克服这一挑战的有力工具，因为它允许将Ox-PTM位点特异性掺入翻译的蛋白质中。然后可以严格表征所得均匀修饰的蛋白质产物的各个Ox-PTM的作用。我们概述了GCE的优点和缺点，因为它们涉及到氧化应激和Ox-PTM领域。概述了已被遗传编码的Ox-PTM和GCE的研究Ox-PTM的应用，包括抗体验证和治疗开发，进行了描述。
Posttranslational modifications resulting from oxidation of proteins (Ox-PTMs) are present intracellularly under conditions of oxidative stress as well as basal conditions. In the past, these modifications were thought to be generic protein damage, but it has become increasingly clear that Ox-PTMs can have specific physiological effects. It is an arduous task to distinguish between the two cases, as multiple Ox-PTMs occur simultaneously on the same protein, convoluting analysis. Genetic code expansion (GCE) has emerged as a powerful tool to overcome this challenge as it allows for the site-specific incorporation of an Ox-PTM into translated protein. The resulting homogeneously modified protein products can then be rigorously characterized for the effects of individual Ox-PTMs. We outline the strengths and weaknesses of GCE as they relate to the field of oxidative stress and Ox-PTMs. An overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs, including antibody validation and therapeutic development, is described.
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