Send to

Choose Destination
Chem Biol. 2015 Jul 23;22(7):965-75. doi: 10.1016/j.chembiol.2015.06.010. Epub 2015 Jul 9.

Site-Specific Proteomic Mapping Identifies Selectively Modified Regulatory Cysteine Residues in Functionally Distinct Protein Networks.

Author information

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA.
Department of Agricultural Biotechnology, Akdeniz University, Antalya 07985, Turkey.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:


S-Acylation, S-glutathionylation, S-nitrosylation, and S-sulfenylation are prominent, chemically distinct modifications that regulate protein function, redox sensing, and trafficking. Although the biological significance of these modifications is increasingly appreciated, their integration in the proteome remains unknown. Novel mass spectrometry-based technologies identified 2,596 predominately unique sites in 1,319 mouse liver proteins under physiological conditions. Structural analysis localized the modifications in unique, evolutionary conserved protein segments, outside commonly annotated functional regions. Contrary to expectations, propensity for modification did not correlate with biophysical properties that regulate cysteine reactivity. However, the in vivo chemical reactivity is fine-tuned for specificity, demonstrated by the nominal complementation between the four modifications and quantitative proteomics which showed that a reduction in S-nitrosylation is not correlated with increased S-glutathionylation. A comprehensive survey uncovered clustering of modifications within biologically related protein networks. The data provide the first evidence for the occurrence of distinct, endogenous protein networks that undergo redox signaling through specific cysteine modifications.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center