Format

Send to

Choose Destination
Cell. 2014 Oct 23;159(3):623-34. doi: 10.1016/j.cell.2014.09.032. Epub 2014 Oct 16.

Target-selective protein S-nitrosylation by sequence motif recognition.

Author information

1
Department of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
2
Mass Spectrometry Laboratory for Protein Sequencing, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
3
Department of Molecular Cardiology, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
4
Department of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: foxp@ccf.org.

Abstract

S-nitrosylation is a ubiquitous protein modification emerging as a principal mechanism of nitric oxide (NO)-mediated signal transduction and cell function. S-nitrosylases can use NO synthase (NOS)-derived NO to modify selected cysteines in target proteins. Despite proteomic identification of over a thousand S-nitrosylated proteins, few S-nitrosylases have been identified. Moreover, mechanisms underlying site-selective S-nitrosylation and the potential role of specific sequence motifs remain largely unknown. Here, we describe a stimulus-inducible, heterotrimeric S-nitrosylase complex consisting of inducible NOS (iNOS), S100A8, and S100A9. S100A9 exhibits transnitrosylase activity, shuttling NO from iNOS to the target protein, whereas S100A8 and S100A9 coordinately direct site selection. A family of proteins S-nitrosylated by iNOS-S100A8/A9 were revealed by proteomic analysis. A conserved I/L-X-C-X2-D/E motif was necessary and sufficient for iNOS-S100A8/A9-mediated S-nitrosylation. These results reveal an elusive parallel between protein S-nitrosylation and phosphorylation, namely, stimulus-dependent posttranslational modification of selected targets by primary sequence motif recognition.

PMID:
25417112
PMCID:
PMC4243042
DOI:
10.1016/j.cell.2014.09.032
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

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