Solution structure of human acidic fibroblast growth factor and interaction with heparin-derived hexasaccharide

Fibroblast growth factors (FGFs) bind to extracellular matrices, especially heparin-like carbohydrates of heparan-sulfate proteoglycans which stabiliz e FGFs to protect against inactivation by heat, acid, proteolysis and oxida tion. Moreover, binding of FGFs to cell surface proteoglycans promotes to f orm oligomers, which is essential for receptor oligomerization and activati on. In the present study, we determined the solution structure of acidic FG F using a series of triple resonance multi-dimensional NMR experiments and simulated annealing calculations. Furthermore, we prepared the sample compl exed with a heparin-derived hexasaccharide which is a minimum unit for aFGF binding. From the chemical shift differences between free aFGF and aFGF-he parin complex, we concluded that the major heparin binding site was located on the regions 110-131 and 17-21. The binding sites are quite similar to t hose observed for bFGF-heparin hexasaccharide complex, showing that both FG Fs recognize heparin-oligosaccharides in a similar manner.