Characterization of a Heparan Sulfate Octasaccharide that Binds to Herpes Simplex Viral Type 1 Glycoprotein D
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Authors
Liu, J.
Shriver, Z.
Pope, R.M.
Thorp, S.C.
Raska, C.S.
Yoshida, K.
Eisenberg, R.J.
Cohen, G.
Linhardt, Robert J.
Sasisekharan, R.
Issue Date
2002
Type
Article
Language
en_US
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Herpes simplex virus type 1 utilizes cell surface heparan sulfate as receptors to infect target cells. The unique heparan sulfate saccharide sequence offers the binding site for viral envelope proteins and plays critical roles in assisting viral infections. A specific 3-O-sulfated heparan sulfate is known to facilitate the entry of herpes simplex virus 1 into cells. The 3-O-sulfated heparan sulfate is generated by the heparan sulfate d-glucosaminyl-3-O-sulfotransferase isoform 3 (3-OST-3), and it provides binding sites for viral glycoprotein D (gD). Here, we report the purification and structural characterization of an oligosaccharide that binds to gD. The isolated gD-binding site is an octasaccharide, and has a binding affinity to gD around 18 microm, as determined by affinity coelectrophoresis. The octasaccharide was prepared and purified from a heparan sulfate oligosaccharide library that was modified by purified 3-OST-3 enzyme. The molecular mass of the isolated octasaccharide was determined using both nanoelectrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry. The results from the sequence analysis suggest that the structure of the octasaccharide is a heptasulfated octasaccharide. The proposed structure of the octasaccharide is DeltaUA-GlcNS-IdoUA2S-GlcNAc-UA2S-GlcNS-IdoUA2S-GlcNH(2)3S6S. Given that the binding of 3-O-sulfated heparan sulfate to gD can mediate viral entry, our results provide structural information about heparan sulfate-assisted viral entry.
Description
Journal of Biological Chemistry, 277,33456-33467
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Characterization of a Heparan Sulfate Octasaccharide that Binds to Herpes Simplex Viral Type 1 Glycoprotein D, J. Liu, Z. Shriver, R.M. Pope, S.C. Thorp, C.S. Raska, K. Yoshida, R.J. Eisenberg, G. Cohen, R.J. Linhardt, R. Sasisekharan, Journal of Biological Chemistry, 277,33456-33467. 2002.
Publisher
Elsevier