Proteomics insights into deregulated protein S-nitrosylation and disease

Abstract

Nitric oxide (NO) can modulate cell function by the coupling of a nitroso moiety to a reactive cysteine in target proteins leading to the formation of a S-nitrosothiol (SNO), a process commonly known as S-nitrosylation. Aberrant S-nitrosylation of proteins, caused by altered production of NO and/or impaired SNO homeostasis, constitutes a mechanism that has been recently postulated in numerous pathophysiological settings. The thiol microenvironment, cellular redox environment, and activity of transnitrosylases and denitrosylases have been proposed as determinant factors for the specificity of S-nitrosylation. A number of methodological approaches have recently been developed for the proteomic identification of S-nitrosylated proteins and/or the identification of specific sites of nitrosylation. This review will consider novel aspects of SNO homeostasis and S-nitrosylation, the latest proteomic methods for the identification of S-nitrosylated cysteines in proteins, and how these novel technologies will impact our current knowledge of the role of deregulated S-nitrosylation in disease.

Keywords::

• biotin-switch technique
• cysteine modification
• denitrosylases
• disease
• nitric oxide
• nitrosoproteome
• nitrosylases
• post-translational
• proteomics

Financial & competing interests disclosure

The authors are supported by the Andalusian Government (grant JA0230/09 from the Consejería de Salud de la Junta de Andalucía) and the Spanish Government (grant FIS 10/00428 from the Programa de Promoción de la Investigación en Salud del Ministerio de Ciencia e Innovación). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.