Li Xiaolu, Zhang Tong, Day Nicholas J, Feng Song, Gaffrey Matthew J, Qian Wei-Jun
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Antioxidants (Basel). 2022 Nov 17;11(11):2272. doi: 10.3390/antiox11112272.
Protein S-glutathionylation (SSG) is a reversible post-translational modification (PTM) featuring the conjugation of glutathione to a protein cysteine thiol. SSG can alter protein structure, activity, subcellular localization, and interaction with small molecules and other proteins. Thus, it plays a critical role in redox signaling and regulation in various physiological activities and pathological events. In this review, we summarize current biochemical and analytical approaches for characterizing SSG at both the proteome level and at individual protein levels. To illustrate the mechanism underlying SSG-mediated redox regulation, we highlight recent examples of functional and structural consequences of SSG modifications. Finally, we discuss the analytical challenges in characterizing SSG and the thiol PTM landscape, future directions for understanding of the role of SSG in redox signaling and regulation and its interplay with other PTMs, and the potential role of computational approaches to accelerate functional discovery.
蛋白质S-谷胱甘肽化（SSG）是一种可逆的翻译后修饰（PTM），其特征是谷胱甘肽与蛋白质半胱氨酸硫醇结合。SSG可改变蛋白质结构、活性、亚细胞定位以及与小分子和其他蛋白质的相互作用。因此，它在各种生理活动和病理事件的氧化还原信号传导和调节中起关键作用。在本综述中，我们总结了目前在蛋白质组水平和单个蛋白质水平上表征SSG的生化和分析方法。为了阐明SSG介导的氧化还原调节的潜在机制，我们重点介绍了SSG修饰的功能和结构后果的最新实例。最后，我们讨论了表征SSG和硫醇PTM格局的分析挑战、理解SSG在氧化还原信号传导和调节中的作用及其与其他PTM相互作用的未来方向，以及计算方法在加速功能发现方面的潜在作用。
