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

Post-translational protein modification by tyrosine sulfation has an important role in extracellular protein–protein interactions. The protein tyrosine sulfation reaction is catalysed by the Golgi enzyme called the tyrosylprotein sulfotransferase. To date, no crystal structure is available for tyros...

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Bibliographic Details
Published in:	Nature communications Vol. 4; no. 1; p. 1572
Main Authors:	Teramoto, Takamasa, Fujikawa, Yukari, Kawaguchi, Yoshirou, Kurogi, Katsuhisa, Soejima, Masayuki, Adachi, Rumi, Nakanishi, Yuichi, Mishiro-Sato, Emi, Liu, Ming-Cheh, Sakakibara, Yoichi, Suiko, Masahito, Kimura, Makoto, Kakuta, Yoshimitsu
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 2013 Nature Publishing Group
Subjects:	631/45/173 631/45/535 Adenosine Diphosphate - chemistry Adenosine Diphosphate - metabolism Binding Sites Biocatalysis Catalytic Domain Crystallography, X-Ray Humanities and Social Sciences Humans Membrane Proteins - chemistry Membrane Proteins - metabolism Models, Molecular multidisciplinary Mutant Proteins - chemistry Mutant Proteins - metabolism Peptides - chemistry Peptides - metabolism Protein Multimerization Protein Processing, Post-Translational Protein Structure, Secondary Protein-Tyrosine Kinases - chemistry Science Science (multidisciplinary) Static Electricity Structural Homology, Protein Substrate Specificity Sulfates - metabolism Sulfotransferases - chemistry Sulfotransferases - metabolism Tyrosine - chemistry Tyrosine - metabolism
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Summary:	Post-translational protein modification by tyrosine sulfation has an important role in extracellular protein–protein interactions. The protein tyrosine sulfation reaction is catalysed by the Golgi enzyme called the tyrosylprotein sulfotransferase. To date, no crystal structure is available for tyrosylprotein sulfotransferase. Detailed mechanism of protein tyrosine sulfation reaction has thus remained unclear. Here we present the first crystal structure of the human tyrosylprotein sulfotransferase isoform 2 complexed with a substrate peptide (C4P5Y3) derived from complement C4 and 3′-phosphoadenosine-5′-phosphate at 1.9 Å resolution. Structural and complementary mutational analyses revealed the molecular basis for catalysis being an S N 2-like in-line displacement mechanism. Tyrosylprotein sulfotransferase isoform 2 appeared to recognize the C4 peptide in a deep cleft by using a short parallel β-sheet type interaction, and the bound C4P5Y3 forms an L-shaped structure. Surprisingly, the mode of substrate peptide recognition observed in the tyrosylprotein sulfotransferase isoform 2 structure resembles that observed for the receptor type tyrosine kinases. The post-translational protein modification tyrosine sulfation is catalysed by tyrosylprotein sulfotransferase (TPST). Teramoto et al . present the first crystal structure of the human TPST isoform 2 complexed with a substrate peptide derived from complement C4 and 3′phosphoadenosine-5′-phosphate, revealing the molecular basis of catalysis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 T.T performed experiments (protein production, crystallization, X-ray data collection and structure determination), analyzed data, and prepared the manuscript; Y.F, Y.K, M.S. R.A. Y.N performed experiments (protein production, crystallization, binding inhibition assay), analyzed data; K.K, E. M-S, Y.S. performed experiments (enzymological measurements), analyzed data; M-C. L, M.S, M.K analyzed data and prepared the manuscript; Y.K. devised the project, performed experiments (X-ray data collection and structure determination), analyzed data, and wrote the paper. AUTHOR CONTRIBUTIONS
ISSN:	2041-1723 2041-1723
DOI:	10.1038/ncomms2593