Characterization of heparan sulfate oligosaccharides that bind to hepatocyte growth factor.
Proteoglycans from rat liver had the ability to bind hepatocyte growth factor (HGF). Digestion of the proteoglycans with heparitinase resulted in the complete loss of the activity, while the digestion with chondroitinase ABC had no effect. Heparan sulfate (HS)-conjugated gel also bound HGF, and the binding was competitively inhibited by heparin and bovine liver HS, but not by Engelbreth-Holm-Swarm sarcoma HS, pig aorta HS, or other glycosaminoglycans, suggesting the specific structural domain in HS for the binding of HGF. Among limited digests with heparitinase I of bovine liver HS, octasaccharide is the minimal size to bind HGF. Comparison of the disaccharide unit compositions revealed a marked difference in IdoA(2SO4)-GlcNSO3(6SO4) unit between the bound and unbound octasaccharides. The contents of this disaccharide unit were calculated to be 2 mol/mol for the bound octasaccharide but 1 mol/mol for the unbound one. Considering both the substrate specificity and properties of heparitinase I, the above results suggest that the bound octasaccharide should contain two units of IdoA(2SO4)-GlcNSO3(6SO4) contiguously or alternately in the vicinity of the reducing end. The bound decasaccharide was more than 20 times as active as the unbound one with regard to the ability to release HGF bound to rat liver HS proteoglycan. The ability was comparable to the one-fourth of that of heparin.
D000818:Animals; D002240:Carbohydrate Sequence; D002417:Cattle; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats
D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D017228:Hepatocyte Growth Factor; D009844:Oligosaccharides; D011509:Proteoglycans