The SNO-proteome: causation and classifications

Abstract

Cell signaling is a complex and highly regulated process. Post-translational modifications of proteins serve to sense and transduce cellular signals in a precisely coordinated manner. It is increasingly recognized that protein S-nitrosylation, the addition of a nitric oxide group to cysteine thiols, serves an important role in a wide range of signaling pathways. In spite of the large number of SNO-proteins now identified (∼1000), the observed specificity of S-nitrosylation in terms of target proteins and specific cysteines within modified proteins is incompletely understood. Here we review the progress made in S-nitrosylation detection methods that have facilitated the study of the SNO-proteome under physiological and pathophysiological conditions, and some factors important in determining the SNO-proteome. Classification schemes for emergent denitrosylases and prospective 'protein S-nitrosylases' are provided.

Figure 1. S-nitrosylation of a crucial cysteine in the pleckstrin homology domain regulates dynamin multimerization

The S-nitrosylated Cys607 lies in a hydrophobic pocket (so-called “hydrophobic core” of the pleckstrin homology domain), which contains aromatic side-chains and an acid-base motif within a 6Å radius (“acid-base/hydrophobic” motif). The residues that form the proposed S-nitrosylation motif are conserved in mammalian dynamins and are highlighted in the pleckstrin homology domain sequence.