Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1.

Abstract

Heparan sulfate 3-O-sulfotransferase transfers sulfate to the 3-OH position of a glucosamine residue of heparan sulfate (HS) to form 3-O-sulfated HS. The 3-O-sulfated glucosamine residue contributes to two important biological functions of HS: binding to antithrombin and thereby carrying anticoagulant activity, and binding to herpes simplex viral envelope glycoprotein D to serve as an entry receptor for herpes simplex virus 1. A total of five HS 3-O-sulfotransferase isoforms were reported previously. Here we report the isolation and characterization of a novel HS 3-O-sulfotransferase isoform, designated as HS 3-O-sulfotransferase isoform 5 (3-OST-5). 3-OST-5 cDNA was isolated from a human placenta cDNA library and expressed in COS-7 cells. The disaccharide analysis of 3-OST-5-modified HS revealed that 3-OST-5 generated at least three 3-O-sulfated disaccharides as follows: IdoUA2S-AnMan3S, GlcUA-AnMan3S6S, and IdoUA2S-AnMan3S6S. Transfection of the plasmid expressing 3-OST-5 rendered wild type Chinese hamster ovary cells susceptible to the infection by herpes simplex virus 1, suggesting that 3-OST-5-modified HS serves as an entry receptor for herpes simplex virus 1. In addition, 3-OST-5-modified HS bound to herpes simplex viral envelope protein glycoprotein D. Furthermore, we found that 3-OST-5-modified HS also bound to antithrombin, suggesting that 3-OST-5 also produces anticoagulant HS. In summary, our results indicate that a new member of 3-OST family generates both anticoagulant HS and an entry receptor for herpes simplex virus 1. These results provide a new insight regarding the mechanism for the biosynthesis of biologically active HS.

• Authors: Guoqing Xia, Jinghua Chen, Vaibhav Tiwari, Wujian Ju, Jin-Ping Li, Anders Malmstrom, Deepak Shukla, Jian Liu
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 40 Pg. 37912-9 (Oct 04 2002) ISSN: 0021-9258 [Print] United States
• PMID: 12138164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antithrombins
• DNA Primers
• DNA, Complementary
• Disaccharides
• Isoenzymes
• Receptors, Virus
• Recombinant Proteins
• Sulfotransferases
• heparitin sulfotransferase

Topics

• Animals
• Antithrombins (metabolism)
• Base Sequence
• Binding Sites
• Cell Line
• Chromatography, High Pressure Liquid
• DNA Primers
• DNA, Complementary (genetics)
• Disaccharides (metabolism)
• Herpesvirus 1, Human (physiology)
• Humans
• Isoenzymes (metabolism)
• Mice
• Molecular Sequence Data
• Polymerase Chain Reaction
• Receptors, Virus (chemistry, metabolism)
• Recombinant Proteins (metabolism)
• Sequence Alignment
• Sequence Homology, Amino Acid
• Spodoptera
• Substrate Specificity
• Sulfotransferases (genetics, metabolism)
• Transfection