Couvertier Shalise M, Zhou Yani, Weerapana Eranthie
Boston College, Chestnut Hill, MA 02467, USA.
Boston College, Chestnut Hill, MA 02467, USA.
Biochim Biophys Acta. 2014 Dec;1844(12):2315-30. doi: 10.1016/j.bbapap.2014.09.024. Epub 2014 Oct 5.
The unique combination of nucleophilicity and redox-sensitivity that is characteristic of cysteine residues results in a variety of posttranslational modifications (PTMs), including oxidation, nitrosation, glutathionylation, prenylation, palmitoylation and Michael adducts with lipid-derived electrophiles (LDEs). These PTMs regulate the activity of diverse protein families by modulating the reactivity of cysteine nucleophiles within active sites of enzymes, and governing protein localization between soluble and membrane-bound forms. Many of these modifications are highly labile, sensitive to small changes in the environment, and dynamic, rendering it difficult to detect these modified species within a complex proteome. Several chemical-proteomic platforms have evolved to study these modifications and enable a better understanding of the diversity of proteins that are regulated by cysteine PTMs. These platforms include: (1) chemical probes to selectively tag PTM-modified cysteines; (2) differential labeling platforms that selectively reveal and tag PTM-modified cysteines; (3) lipid, isoprene and LDE derivatives containing bioorthogonal handles; and (4) cysteine-reactivity profiling to identify PTM-induced decreases in cysteine nucleophilicity. Here, we will provide an overview of these existing chemical-proteomic strategies and their effectiveness at identifying PTM-modified cysteine residues within native biological systems.
半胱氨酸残基所具有的亲核性和氧化还原敏感性的独特组合，导致了多种翻译后修饰（PTM），包括氧化、亚硝化、谷胱甘肽化、异戊二烯化、棕榈酰化以及与脂质衍生亲电试剂（LDE）形成的迈克尔加成物。这些PTM通过调节酶活性位点内半胱氨酸亲核试剂的反应性，以及控制蛋白质在可溶性和膜结合形式之间的定位，来调节多种蛋白质家族的活性。这些修饰中的许多都非常不稳定，对环境中的微小变化敏感且具有动态性，这使得在复杂蛋白质组中检测这些修饰物种变得困难。几种化学蛋白质组学平台已经发展起来，用于研究这些修饰，并能更好地理解受半胱氨酸PTM调节的蛋白质的多样性。这些平台包括：（1）选择性标记PTM修饰半胱氨酸的化学探针；（2）选择性揭示并标记PTM修饰半胱氨酸的差异标记平台；（3）含有生物正交手柄的脂质、异戊二烯和LDE衍生物；以及（4）用于识别PTM诱导的半胱氨酸亲核性降低的半胱氨酸反应性分析。在这里，我们将概述这些现有的化学蛋白质组学策略及其在天然生物系统中识别PTM修饰半胱氨酸残基的有效性。
