Department of Structural and Medicinal Biochemistry, University of Duisburg-Essen, Universitaetsstrasse 2, 45141 Essen, Germany.
Department of Developmental Biology, University of Duisburg-Essen, Universitaetsstrasse 2, 45141 Essen, Germany.
J Mol Biol. 2015 Mar 27;427(6 Pt B):1404-1412. doi: 10.1016/j.jmb.2015.01.021. Epub 2015 Feb 7.
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.
蛋白质的酪氨酸硫酸化是一种重要的翻译后修饰，被证明在许多膜相关或细胞外过程中发挥作用，如病毒进入、血液凝固、抗体介导的免疫反应、炎症和卵子受精。唯一能够将硫酸基团从 3'-磷酸腺苷-5'-磷酸硫酸转移到酪氨酸残基上的两种人类酶，TPST1 和 TPST2，与反式高尔基体隔室的膜锚定，催化结构域朝向腔。与中高尔基体酶的相对较好研究的组织相比，反式高尔基体转移酶的组织仍然难以捉摸。尽管酪氨酸蛋白硫酸转移酶已知在高尔基体膜中以同源二聚体的形式存在，但这种组织水平可能只代表与整个画面相关的一个小拼图。在这里，我们报告了 TPST1/TPST2 异源二聚体的形成以及 TPST1 或 TPST2 与α-2,6-唾液酸转移酶之间的新相互作用，表明酪氨酸蛋白硫酸转移酶的更高组织水平可能有助于底物选择性和/或蛋白质的多种翻译后修饰的有效组织。
