2. Academic Validation
  3. Target-selective protein S-nitrosylation by sequence motif recognition

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.
Jie Jia 1,  Abul Arif 1,  Fulvia Terenzi 1,  Belinda Willard 2,  Edward F Plow 3,  Stanley L Hazen 1,  Paul L Fox 4
Affiliations

Affiliations

  • 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: [email protected].
PMID: 25417112 DOI: 10.1016/j.cell.2014.09.032
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.

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