Raju Karthik, Doulias Paschalis-Thomas, Tenopoulou Margarita, Greene Jennifer L, Ischiropoulos Harry
Department of Pediatrics, Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
Biochim Biophys Acta. 2012 Jun;1820(6):684-8. doi: 10.1016/j.bbagen.2011.05.009. Epub 2011 May 30.
A biochemical pathway by which nitric oxide accomplishes functional diversity is the specific modification of protein cysteine residues to form S-nitrosocysteine. This post-translational modification, S-nitrosylation, impacts protein function, interactions and location. However, comprehensive studies exploring protein signaling pathways or interrelated protein clusters that are regulated by S-nitrosylation have not been performed on a global scale.
To provide insights to these important biological questions, sensitive, validated and quantitative proteomic approaches are required. This review summarizes current approaches for the global identification of S-nitrosylated proteins.
The application of novel methods for identifying S-nitrosylated proteins, especially when combined with mass-spectrometry based proteomics to provide site-specific identification of the modified cysteine residues, promises to deliver critical clues for the regulatory role of this dynamic posttranslational modification in cellular processes.
Though several studies have established S-nitrosylation as a regulator of protein function in individual proteins, the biological chemistry and the structural elements that govern the specificity of this modification in vivo are vastly unknown. Additionally, a gap in knowledge exists concerning the potential global regulatory role(s) this modification may play in cellular physiology. By further studying S-nitrosylation at a global scale, a greater appreciation of nitric oxide and protein S-nitrosylation in cellular function can be achieved. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.
一氧化氮实现功能多样性的一条生化途径是对蛋白质半胱氨酸残基进行特异性修饰以形成S-亚硝基半胱氨酸。这种翻译后修饰，即S-亚硝基化，会影响蛋白质的功能、相互作用及定位。然而，尚未在全球范围内开展全面研究来探索受S-亚硝基化调控的蛋白质信号通路或相关蛋白质簇。
为深入了解这些重要的生物学问题，需要灵敏、经过验证的定量蛋白质组学方法。本综述总结了目前用于全面鉴定S-亚硝基化蛋白质的方法。
应用鉴定S-亚硝基化蛋白质的新方法，尤其是与基于质谱的蛋白质组学相结合以提供修饰半胱氨酸残基的位点特异性鉴定时，有望为这种动态翻译后修饰在细胞过程中的调控作用提供关键线索。
尽管多项研究已确定S-亚硝基化是单个蛋白质中蛋白质功能的调节剂，但体内控制这种修饰特异性的生物化学和结构元件仍知之甚少。此外，对于这种修饰在细胞生理学中可能发挥的潜在全局调控作用，也存在知识空白。通过在全球范围内进一步研究S-亚硝基化，可以更深入地了解一氧化氮和蛋白质S-亚硝基化在细胞功能中的作用。本文是名为“S-亚硝基化对细胞过程的调控”的特刊的一部分。
