Binding of interferon-gamma to heparan sulfate is restricted to the heparin-like domains and involves carboxylic--but not N-sulfated--groups.
Interferon-gamma binds to the glycosaminoglycan part of basement membrane proteoglycan. To obtain a greater insight into this interaction, different glycosaminoglycans and their subfractions were used in various binding assays. High affinity binding occurs with heparin and heparan sulfate only, the latter being the predominant basement membrane glycosaminoglycan. Furthermore, using heparan sulfate and heparin treated with heparinases I and III, we have shown that the interferon-gamma binding sites are localized on the N-sulfated glucosamine rich domains of the molecule. Interestingly, interferon-gamma and fibroblast growth factor compete for the same binding domain on heparan sulfate, although they are unrelated proteins. This last point is discussed in the light of the conformational flexibility of the glycosaminoglycan molecules.
Lortat-Jacob
H
H
Institut Pasteur de Lyon, CNRS URA 1459, France.
Grimaud
J A
JA
D001665:Binding Sites; D002264:Carboxylic Acids / Q000378:metabolism*; D005966:Glucuronidase; D006025:Glycosaminoglycans / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D011994:Recombinant Proteins; D013431:Sulfates / Q000378:metabolism; D000099175:Heparanase
D002264:Carboxylic Acids; D005966:Glucuronidase; D006025:Glycosaminoglycans; D006026:Glycoside Hydrolases; D006493:Heparin; D006497:Heparan Sulfate; D007371:Interferon-gamma; D011994:Recombinant Proteins; D013431:Sulfates; D000099175:Heparanase