title: Binding of heparin to basic fibroblast growth factor induces a conformational change.
abstract: The binding of heparin to basic fibroblast growth factor (bFGF) induces a small but highly reproducible conformational change observable in the amide I region of the protein's infrared spectrum. The observed spectral changes suggest that the conformational change is highly localized most likely in the beta-turn regions of the bFGF molecule. Heparan sulfate, a component of the endothelial extracellular matrix, was also observed to bind to bFGF and induce a similar conformational change to that observed for heparin. Further, sucrose octasulfate, a compound which mimics the effects of heparin biologically, was also observed to induce this same conformational change. This spectroscopically observable change has allowed us to probe the functional determinants necessary for heparin to bind the bFGF and to induce the observed conformational change. We have determined the effects of binding of various monomeric and polymeric, sulfated and nonsulfated glycosaminoglycans and carbohydrate compounds. The results indicate that the binding of heparin involves highly specific interactions. Further, heparin was observed to greatly increase the thermal stability of bFGF, raising the Tm by 25 degrees C. Sucrose octasulfate was also able to enhance the thermal stability of bFGF, but not to the same extent as heparin.
authors.affiliation: Protein Chemistry Department, Amgen Inc., Thousand Oaks, California 91320.
authors.forename: S J
authors.initials: SJ
authors.lastname: Prestrelski
authors.forename: G M
authors.initials: GM
authors.lastname: Fox
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013055:Spectrophotometry, Infrared
chemical_list: D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin