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

Article Details

Citation

Jia J, Arif A, Terenzi F, Willard B, Plow EF, Hazen SL, Fox PL

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

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

PubMed ID
25417112 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Nitric oxide synthase, inducibleP35228Details
Glyceraldehyde-3-phosphate dehydrogenaseP04406Details
Annexin A5P08758Details
VimentinP08670Details
Protein S100-A8P05109Details
Protein S100-A9P06702Details