Heterodimers of Tyrosylprotein Sulfotransferases Suggest Existence of a Higher Organization Level of Transferases in the Membrane of the trans-Golgi Apparatus

Tyrosine sulfation of proteins is an important post-translational modification shown to play a role in many membrane-associated or extracellular processes such as virus entry, blood clotting, antibody-mediated immune response, inflammation and egg fecundation. The sole two human enzymes that transfer sulfate moieties from 3′-phospho-adenosine-5′-phospho-sulfate onto tyrosine residues, TPST1 and TPST2, are anchored to the membranes of the trans-Golgi compartment with the catalytic domain oriented to the lumen. In contrast to the relatively well studied organization of medial Golgi enzymes, the organization of trans-Golgi transferases remains elusive. Although tyrosylprotein sulfotransferases are known to exist as homodimers in the Golgi membranes, this organization level may represent only a small piece of a puzzle that is linked to the entire picture. Here we report the formation of TPST1/TPST2 heterodimers and a novel interaction between either TPST1 or TPST2 and the α-2,6-sialyltransferase, indicating a higher organization level of tyrosylprotein sulfotransferases that may serve for substrate selectivity and/or effective organization of multiple post-translational modification of proteins. [Display omitted] •The exact tyrosine sulfation coding and patterning by tyrosylprotein sulfotransferases is still inchoately understood.•Using bi-molecular fluorescence complementation, we studied organization of these sulfotransferases in the trans-Golgi apparatus.•We found dimerization/oligomerization of these protein sulfotransferases with sialyltransferases.•This observation discloses a new aspect of the determinants of protein sulfation coding.