Three-dimensional structure of human basic fibroblast growth factor, a structural homolog of interleukin 1β

Abstract

The three-dimensional structure of the 146-residue form of human basic fibroblast growth factor (bFGF), expressed as a recombinant protein in yeast, has been determined by x-ray crystallography to a resolution of 1.8 Å. bFGF is composed entirely of β-sheet structure, comprising a three-fold repeat of a four-stranded antiparallel β-meander. The topology of bFGF is identical to that of interleukin 1β, showing that although the two proteins share only 10% sequence identity, bFGF, interleukin 1, and their homologs comprise a family of structurally related mitogenic factors. Analysis of the three-dimensional structure in light of functional studies of bFGF suggests that the receptor binding site and the positively charged heparin binding site correspond to adjacent but separate loci on the β-barrel.