Though bFGF contains four Cysteines, none of them are involved in disulfide bonding. Indeed, all four residues can be replaced with serines without loss of activity. Click button to see them

Residues 106-115 comprise parts of two beta sheets and a loop outside of the barrel and are thought to be the high-affinity receptor binding site. Click button to see them. Within this loop, Tyr114 and Trp115 appear to be the most critical amino acids for strong binding. They are also conserved in IL-1beta, a structural homolog. Click button to see them.

Thr112 can be phosphorylated by Protein Kinase A, increasing the receptor binding affinity by nearly 10-fold. Click button to see it.

Arg107 and Arg109 (in red) are possible ligands for the phosphorylated threonine. Click button to see them. This offers insight to the mechanism of action: since Arg109 (red) naturally forms a salt bridge with Glu59 (yellow), addition of a phosphate group would break this link and cause a conformational change, thereby making the receptor site fit the FGF receptor better. Click button to see Arg109 and Glu57.

Heparin, a molecule that protects bFGF from degradation and denaturation while enhancing its binding affinity, is thought to interact with bFGF at as many as three different sites. The sulfites in heparin may link Lys119 and Lys129 (red), or Arg120 and Lys125 (green). Arg39 (yellow) has also shown binding activity, though heprain has not been shown to link it to any other residue. Click button to see these sites.

References:

Zhang, J., Cousens, L., Barr, P., amd Spang, S. (1991) Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1 beta. PNAS vol.88, 3446-3450.

PDB. 2005. <http://www.rcsb.org/pdb/> Accessed 4-03-05.