Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus

J Mol Biol. 2015 Mar 27;427(6 Pt B):1404-1412. doi: 10.1016/j.jmb.2015.01.021. Epub 2015 Feb 7.

Abstract

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.

Keywords: BiFC; ST6; SiaT; TPST; dimerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Membrane / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism*
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Sialyltransferases / chemistry*
  • Sialyltransferases / metabolism*
  • Sulfotransferases / chemistry*
  • Sulfotransferases / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Membrane Proteins
  • tyrosine O-sulfate
  • Tyrosine
  • Sialyltransferases
  • beta-D-galactoside alpha 2-6-sialyltransferase
  • Sulfotransferases
  • TPST2 protein, human
  • protein-tyrosine sulfotransferase