Heparan sulfate glycomics: towards systems biology strategies

2010 ◽  
Vol 38 (5) ◽  
pp. 1356-1360 ◽  
Author(s):  
Jeremy E. Turnbull
Keyword(s):  
Systems Biology ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Biological Functions ◽  
Combined Application ◽  
Cellular Events ◽  
Structure Activity ◽  
Future Potential ◽  
Heparan Sulfates ◽  
Molecular Code

HSs (heparan sulfates) are a complex family of cell-surface and matrix polysaccharides that have diverse biological functions, underpinned by structurally diverse patterns of backbone chain modification, especially by sulfate groups. These variant structures represent a molecular code, the ‘heparanome’, that confers the ability to interact selectively with a wide interactome of proteins, the ‘heparactome’, and thereby influence a network of cellular events. It is becoming increasingly apparent that understanding the structure–activity relationships of these enigmatic molecules requires the development of a holistic systems biology view of their structure and interactions. In the present paper, I describe some of the new tools available to realize this strategy, and discuss the future potential for the combined application of glycomics and other ‘-omics’ approaches to define the molecular code of the heparanome.

scholarly journals The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus infectivity

2019 ◽  
Author(s):  
Mohammad H. Hasan ◽  
Rinkuben Parmar ◽  
Quntao Liang ◽  
Hong Qiu ◽  
Vaibhav Tiwari ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Virus Entry ◽  
Degree Of Polymerization ◽  
Convincing Evidence ◽  
Host Cells ◽  
Virus Infectivity ◽  
Cmv Infection ◽  
Virus Binding ◽  
Heparan Sulfates

AbstractHerpesviruses attach to host cells by interacting with cell surface heparan sulfate (HS) proteoglycans prior to specific coreceptor engagement which culminates in virus-host membrane fusion and virus entry. Interfering with HS-herpesvirus interactions results in significant reduction in virus infectivity indicating that HS play important roles in initiating virus entry. In this study, we provide convincing evidence that specific sulfations as well as the degree of polymerization (dp) of HS govern human cytomegalovirus (CMV) infection and binding by following line of evidences. First, purified CMV extracellular virions preferentially bound to the sulfated longer chain of HS on a glycoarray compared to unsulfated glycosaminoglycans and shorter chain unsulfated HS. Second, the fraction of glycosaminoglycans (GAG) displaying higherdpand sulfation had a major impact on CMV infectivity and titers. Finally, cell lines knocked out for specific sulfotransferases Glucosaminyl 3-O-sulfotransferase (3-O-ST-1 and −4 and double −1/4) produced significantly reduced CMV titers compared to wild-type cells. Similarly, a peptide generated against sulfated-HS significantly reduced virus titers compared to the control peptide. Taken together, the above results highlight the significance of the chain length and sulfation patterns of HS in CMV binding and infectivity.ImportanceThe cell surface heparan sulfates (HS) are exploited by multiple viruses as they provide docking sites during cell entry and therefore are a promising target for the development of novel antivirals. In addition, the molecular diversity in HS chains generates unique binding sites for specific ligands and hence offers preferential binding for one virus over other. In the current study several HS mimics were analyzed for their ability to inhibit cytomegalovirus (CMV) infection. The results were corroborated by parallel studies in mutant mouse cells and virus binding to glycoarrays. Combined together, the data suggests that virus particles preferentially attach to specifically modified HS and thus the process is amenable to targeting by specifically designed HS mimics.

scholarly journals Correlation between cell substrate attachment in vitro and cell surface heparan sulfate affinity for fibronectin and collagen.

1983 ◽  
Vol 96 (6) ◽  
pp. 1820-1823 ◽  
Author(s):  
S C Stamatoglou ◽  
J M Keller
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Cell Attachment ◽  
Myeloma Cell ◽  
Collagen Type I ◽  
Type I ◽  
Heparan Sulfates ◽  
Sepharose 4B

Heparan sulfate glycosaminoglycan, isolated from the cell surface of nonadhering murine myeloma cells (P3X63-Ag8653), does not bind to plasma fibronectin, but binds partially to collagen type I, as assayed by affinity chromatography with proteins immobilized on cyanogen bromide-activated Sepharose 4B. Identical results were obtained when myeloma heparan sulfate was cochromatographed, on the same fibronectin and collagen columns, with cell surface heparan sulfates collagen columns, with cell surface heparan sulfates from adhering Swiss mouse 3T3 and SV3T3 cells. These latter heparan sulfates do, however, bind to both fibronectin and collagen, as reported earlier (Stamatoglou, S.C., and J.M. Keller, 1981, Biochim. Biophys. Acta., 719:90-97). Cell adhesion assays established that hydrated collagen substrata can support myeloma cell attachment, but fibronectin cannot. Saturation of the heparan sulfate binding sites on the collagen substrata with heparan sulfate or heparin, prior to cell inoculation, abolished the ability to support cell adhesion, whereas chondroitin 4 sulfate, chondroitin 6 sulfate, and hyaluronic acid had no effect.

scholarly journals Investigation of the biological functions of heparan sulfate using a chemoenzymatic synthetic approach

2021 ◽  
Author(s):  
Zhangjie Wang ◽  
Katelyn Arnold ◽  
Vijay Manohar Dhurandhare ◽  
Yongmei Xu ◽  
Jian Liu
Keyword(s):  
Heparan Sulfate ◽  
Sulfated Polysaccharide ◽  
Synthetic Approach ◽  
Biological Functions ◽  
Animal Kingdom

Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom.

scholarly journals Molecular cloning of the major cell surface heparan sulfate proteoglycan from rat liver.

1992 ◽  
Vol 267 (6) ◽  
pp. 3894-3900
Author(s):  
A Pierce ◽  
M Lyon ◽  
I.N. Hampson ◽  
G.J. Cowling ◽  
J.T. Gallagher
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Molecular Cloning ◽  
Rat Liver ◽  
Heparan Sulfate Proteoglycan ◽  
Sulfate Proteoglycan
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