Tyrosine sulfation as a protein post-translational modification

Abstract

Integration of inorganic sulfate into biological molecules plays an important role in biological systems and is directly involved in the instigation of diseases. Protein tyrosine sulfation (PTS) is a common post-translational modification that was first reported in the literature fifty years ago. However, the significance of PTS under physiological conditions and its link to diseases have just begun to be appreciated in recent years. PTS is catalyzed by tyrosylprotein sulfotransferase (TPST) through transfer of an activated sulfate from 3'-phosphoadenosine-5'-phosphosulfate to tyrosine in a variety of proteins and peptides. Currently, only a small fraction of sulfated proteins is known and the understanding of the biological sulfation mechanisms is still in progress. In this review, we give an introductory and selective brief review of PTS and then summarize the basic biochemical information including the activity and the preparation of TPST, methods for the determination of PTS, and kinetics and reaction mechanism of TPST. This information is fundamental for the further exploration of the function of PTS that induces protein-protein interactions and the subsequent biochemical and physiological reactions.

Figure 1

Activation of inorganic sulfate and its assimilation in biological systems. The inorganic sulfate is activated in the forms of adenosine-5'-phosphosulfate (APS) and 3'-phospho-adenosine-5'-phosphosulfate (PAPS) by ATP sulfurylase and APS kinase, respectively. Sulfotransferases are known to be responsible for the transfer of activated sulfate to a variety of biological molecules. Alternately, activation of sulfate serves as a route for the reduction and assimilation of the inorganic sulfate into important amino acids.

Figure 2

Protein tyrosine sulfation (PTS) and its biological path. The drawing depicts biochemical processes of sulfate in cell, from the activation of inorganic sulfate, its integration into protein and its effects on protein-protein interaction that induces physiological and pathogenic responses.

Figure 3

Immobilized metal ion affinity chromatography (IMAC-Ga) for the enrichment of sulfated protein. The structures of IMAC-Ga and its coordination with a sulfated tyrosine are shown. Methods for the enrichment of sulfated peptides and proteins are very useful for the detection of PTS that may be low in a cell.