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

  title={Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus.},
  author={Cristina Hartmann-Fatu and Franziska Trusch and Carina N Moll and Irina Michin and Antti Hassinen and Sakari Kellokumpu and Peter Bayer},
  journal={Journal of molecular biology},
  volume={427 6 Pt B},

Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1

Two crystal structures of the human TPST1 complexed with two substrate peptides that are catalysed by human TP ST1 with significantly different efficiencies are reported, providing insight into the sulfation mechanism for these substrates.

GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles

GOLPH3+3L are major COPI adaptors that impinge on most, if not all, of the glycosylation pathways of the Golgi, and interact with the cytoplasmic tails of their clients through membrane-proximal positively-charged residues.

New tools for evaluating protein tyrosine sulfation: tyrosylprotein sulfotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors

A non-radioactive mobility-based enzymatic assay for TPST1 and TPST2, through which the tyrosine sulfation of synthetic fluorescent peptides can be rapidly quantified, and proposes that target-validated protein kinase inhibitors could be repurposed, or redesigned, as more-specific TPST inhibitors to help evaluate the sulfotyrosyl proteome.

From Steroid and Drug Metabolism to Glycobiology, Using Sulfotransferase Structures to Understand and Tailor Function.

This review will focus on the general commonalities of the sulfotransferases, from enzyme structure to catalytic mechanism as well as providing examples into how structural information is being used to either design drugs that inhibit sulfotranferases or to modify the enzymes to improve drug synthesis.

The catalytic reaction mechanism of tyrosylprotein sulfotransferase-1.

The insight into the reaction mechanism of TPST-1 might help with the rational design of transition-state TPST inhibitors, and the comparison of the two methods (metadynamics and potential energy scan) may be helpful for future mechanistic studies.

Glycosyltransferase complexes in eukaryotes: long-known, prevalent but still unrecognized

Accumulated data for their prevalence and potential functional importance for glycosylation focusing mainly on their mutual interactions, the protein domains mediating these interactions, and enzymatic activity changes that occur upon complex formation are summarized.

New tools for evaluating protein tyrosine sulphation: Tyrosyl Protein Sulphotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors

A non-radioactive mobility-based enzymatic assay for TPST1 and TPST2, through which the tyrosine sulphation of synthetic fluorescent peptides can be rapidly quantified, is described, suggesting new starting points to synthesise (or repurpose) small molecule compounds to evaluate biological TPST using chemical biology.

Skeletal Dysplasias Caused by Sulfation Defects

A panoramic view of skeletal dysplasias caused by mutations in genes encoding for transporters or enzymes involved in macromolecular sulfation is presented, allowing the development of targeted therapies aimed at alleviating, preventing, or modifying the disease progression.



Existence of distinct tyrosylprotein sulfotransferase genes: molecular characterization of tyrosylprotein sulfotransferase-2.

An approach to identify the TPST protein, referred to as MSC (modification after substrate crosslinking) labeling, which is based on the crossl linking of a substrate peptide to TPST followed by intramolecular [35S]sulfate transfer from the cosubstrate 3-phosphoadenosine 5'-phosphosulfate (PAPS).

Tyrosylprotein sulfotransferase: purification and molecular cloning of an enzyme that catalyzes tyrosine O-sulfation, a common posttranslational modification of eukaryotic proteins.

The purification of TPST from rat liver microsomes is described based on its affinity for the N-terminal 15 amino acids of PS GL-1, which defines a new class of Golgi sulfotransferases that may catalyze tyrosine O-sulfation of PSGL-1 and other protein substrates involved in diverse physiologic functions including inflammation and hemostasis.

Crystal structure of human tyrosylprotein sulfotransferase-2 reveals the mechanism of protein tyrosine sulfation reaction

The first crystal structure of the human TPST isoform 2 (TPST2) complexed with a substrate peptide derived from complement C4 and 3’-phosphoadenosine-5’ -phosphate (PAP) at 1.9Å resolution is presented.

Golgi N-Glycosyltransferases Form Both Homo- and Heterodimeric Enzyme Complexes in Live Cells*

This work investigates the supramolecular organization of the N-glycosylation pathway in live cells by utilizing the bimolecular fluorescence complementation approach and shows that all four N- glycosylated enzymes tested form Golgi-localized homodimers.

Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence

A detailed analysis of the multiple sulfation reaction of a peptide substrate by TPSTs is provided and provide a structural basis for understanding the role of tyrosine sulfation of CCR5 in HIV-1 coreceptor and chemokine receptor function.

Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface.

Pulse‐chase and immunofluorescence analyses demonstrated that proregion removal occurs in the endoplasmic reticulum and that cleavage may be required for exist from this compartment, and it is shown that pro region removal is necessary but not sufficient for enzyme activation.

Two independent targeting signals in the cytoplasmic domain determine trans‐Golgi network localization and endosomal trafficking of the proprotein convertase furin.

Results obtained on furin mutants with substitutions and deletions of amino acids in the cytoplasmic tail indicate that wild‐type furin is concentrated in the TGN by a mechanism involving two independent targeting signals, which consist of the acidic peptide CPSDSEEDEG783 and the tetrapeptide YKGL765.