Phospho-peptide binding domains in S. cerevisiae model organism.

Protein phosphorylation is one of the main mechanisms by which signals are transmitted in eukaryotic cells, and it plays a crucial regulatory role in almost all cellular processes. In yeast, more than half of the proteins are phosphorylated in at least one site, and over 20,000 phosphopeptides have been experimentally verified. However, the functional consequences of these phosphorylation events for most of the identified phosphosites are unknown. A family of protein interaction domains selectively recognises phosphorylated motifs to recruit regulatory proteins and activate signalling pathways. Nine classes of dedicated modules are coded by the yeast genome: 14-3-3, FHA, WD40, BRCT, WW, PBD, and SH2. The recognition specificity relies on a few residues on the target protein and has coevolved with kinase specificity. In the present study, we review the current knowledge concerning yeast phospho-binding domains and their networks. We emphasise the relevance of both positive and negative amino acid selection to orchestrate the highly regulated outcomes of inter- and intra-molecular interactions. Finally, we hypothesise that only a small fraction of yeast phosphorylation events leads to the creation of a docking site on the target molecule, while many have a direct effect on the protein or, as has been proposed, have no function at all.