Structure of fibroblast growth factor 9 shows a symmetric dimer with unique receptor- and heparin-binding interfaces.
Fibroblast growth factors (FGFs) constitute a family of at least 20 structurally related heparin-binding polypeptides active in regulating cell growth, survival, differentiation and migration. FGF9, originally discovered as a glia-activating factor, shares 30% sequence identity with other FGFs and has a unique spectrum of target-cell specificity. FGF9 crystallized in the tetragonal space group I4(1), with unit-cell parameters a = b = 151.9, c = 117.2 A. The structure of the glycosylated protein has been refined to an R value of 21.0% with R(free) = 24.8%) at 2.6 A resolution. The four molecules in the asymmetric unit are arranged in two non-crystallographic dimers, with the dimer interface composed partly of residues from N- and C-terminal extensions from the FGF core structure. Most of the receptor-binding residues identified in FGF1- and FGF2-receptor complexes are buried in the dimer interface, with the beta8-beta9 loop stabilized in a particular conformation by an intramolecular hydrogen-bonding network. The potential heparin-binding sites are in a pattern distinct from FGF1 and FGF2. The carbohydrate moiety attached at Asn79 has no structural influence.
Department SF, GBF - Gesellschaft für Biotechnologische Forschung, Mascheroder Weg 1, D-38124 Braunschweig, Germany. hjh@gbf.de
H J
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Hecht
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Adar
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Hofmann
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Bogin
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Weich
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Yayon
D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid
C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors; D006493:Heparin