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

Hartmann-Fatu, Christina; Trusch, Franziska; Moll, Carina N; Michin, Irina; Hassinen, Antti; Kellokumpu, Sakari; Bayer, Peter

doi:10.1016/j.jmb.2015.01.021

Cited by 16 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S6 ). A recent report demonstrated that human TPST1 and TPST2 can form heterodimers in vivo 28 . Our results showed the consistency of the dimer interface of human TPSTs, supporting the possibility of heterodimerization of human TPST1 and TPST2.…”

Section: Resultsmentioning

confidence: 99%

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

Tanaka

Nishiyori

Kojo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved. Here, we report two crystal structures of the human TPST1 complexed with two substrate peptides that are catalysed by human TPST1 with significantly different efficiencies. The distinct binding modes found in the two complexes provide insight into the sulfation mechanism for these substrates. The present study provides valuable information describing the molecular mechanism of post-translational protein modifications catalysed by TPSTs.

show abstract

Section: Resultsmentioning

confidence: 99%

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

Tanaka

Nishiyori

Kojo

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In the Golgi also specific tyrosine residues of secreted proteins and peptides are sulfated by tyrosylprotein sulfotransferases (TPST1 and TPST2) [54]. These two enzymes show 67% amino acid identity and use PAPS as obligate sulfate donor.…”

Section: The Sulfation Pathwaymentioning

confidence: 99%

Skeletal Dysplasias Caused by Sulfation Defects

Paganini

Tota

Superti‐Furga

et al. 2020

IJMS

View full text Add to dashboard Cite

Proteoglycans (PGs) are macromolecules present on the cell surface and in the extracellular matrix that confer specific mechanical, biochemical, and physical properties to tissues. Sulfate groups present on glycosaminoglycans, linear polysaccharide chains attached to PG core proteins, are fundamental for correct PG functions. Indeed, through the negative charge of sulfate groups, PGs interact with extracellular matrix molecules and bind growth factors regulating tissue structure and cell behavior. The maintenance of correct sulfate metabolism is important in tissue development and function, particularly in cartilage where PGs are fundamental and abundant components of the extracellular matrix. In chondrocytes, the main sulfate source is the extracellular space, then sulfate is taken up and activated in the cytosol to the universal sulfate donor to be used in sulfotransferase reactions. Alteration in each step of sulfate metabolism can affect macromolecular sulfation, leading to the onset of diseases that affect mainly cartilage and bone. This review presents a panoramic view of skeletal dysplasias caused by mutations in genes encoding for transporters or enzymes involved in macromolecular sulfation. Future research in this field will contribute to the understanding of the disease pathogenesis, allowing the development of targeted therapies aimed at alleviating, preventing, or modifying the disease progression.

show abstract

“…Crosstesting potential interactions between N-and O-glycosyltransferses [41] did not reveal any interacting partners, suggesting that complexes form only between sequentially acting enzymes within the same glycosylation pathway. Very recently, the BiFC approach was used to show interactions between tyrosylprotein sulfotransferases TPST1 and TPST2 [46] with the result that these enzymes formed complexes not only with themselves, but also with STGalT-I, producing either TPST1/ST6Gal-I or TPST2/ ST6Gal-I heteromers. A different type of interaction takes place between GlcNAcT-I and GnT1IPL (Mgat4D) protein in that the latter has no known enzymatic activity and is expressed at high levels in the testicular germ cells [47].…”

Section: Complexes Involved In N-linked Glycans Synthesismentioning

confidence: 99%

“…In addition, the initiating GalNAcT-6 and C1GalT required for the synthesis of the T(F)-antigen were shown to form a hetoromeric complex with each other. The same GalNAcT6 was also found to interact with the core 3 and core 6 forming glycosyltransferases (C3GnT-I, GlcNAcT-I/GlcNAcT-II N-glycan branching H. sapiens [35,40,41] GalT-I/ST6Gal-I and GalT-I/ST3Gal-III Termination of N-glycans H. sapiens [40,41] B3GnT-8/B3GnT-2 Synthesis of polylactosamine H. sapiens [44,45] TPST1/ST6Gal-I, TPST2/ST6Gal-I Tyrosylprotein sulfation/sialylation H. sapiens [46] GlcNAcT-I/GnT1IPL…”

Section: Complexes Involved In O-linked Glycan Synthesismentioning

confidence: 99%

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

Kellokumpu

Hassinen

Glumoff

2015

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Glycosylation is the most common and complex cellular modification of proteins and lipids. It is critical for multicellular life and its abrogation often leads to a devastating disease. Yet, the underlying mechanistic details of glycosylation in both health and disease remain unclear. Partly, this is due to the complexity and dynamicity of glycan modifications, and the fact that not all the players are taken into account. Since late 1960s, a vast number of studies have demonstrated that glycosyltransferases typically form homomeric and heteromeric complexes with each other in yeast, plant and animal cells. To propagate their acceptance, we will summarize here 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. Finally, we will highlight the few existing 3D structures of these enzyme complexes to pinpoint their individual nature and to emphasize that their lack is the main obstacle for more detailed understanding of how these enzyme complexes interact and function in a eukaryotic cell.

show abstract

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

Cited by 16 publications

References 30 publications

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

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

Skeletal Dysplasias Caused by Sulfation Defects

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

Contact Info

Product

Resources

About