Biological Significance and Analysis of Tyrosine Sulfation

Protein tyrosine sulfation is performed by protein tyrosine sulfotransferases in the Golgi apparatus of the cell. Secreted proteins and the extracellular domains of transmembrane proteins may feature this posttranslational modification (PTM) that has been implicated as an important factor in protein–protein and receptor–ligand interactions. While large-scale proteomic studies are performed for numerous PTMs, tyrosine sulfation does not belong to this group as yet. Sulfopeptides still represent a significant challenge since (i) sulfation can be confused with phosphorylation, as the mass difference between the two modifications is only 9 mmu; (ii) the modification is prone to gas-phase elimination both in MS and MS/MS experiments; (iii) no reliable method has been developed for the selective enrichment of sulfopeptides. Here, we present a brief history covering the sulfosites characterized up to date, along with a detailed overview of the methods available for sulfopeptide characterization including efforts to identify potential modification sites by different prediction algorithms.