1QQL

THE CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 7/1 CHIMERA

Summary for 1QQL

• Entry DOI: 10.2210/pdb1qql/pdb
• Related: 1QQK
• Descriptor: Fibroblast growth factor 7, Fibroblast growth factor 1 chimera (2 entities in total)
• Functional Keywords: beta-trefoil, hormone-growth factor complex, hormone/growth factor
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 1
• Total formula weight: 16433.94

Authors

Ye, S.,Luo, Y.,Pelletier, H.,McKeehan, W.L. (deposition date: 1999-06-07, release date: 2000-01-14, Last modification date: 2024-10-02)

Primary citation

Ye, S.,Luo, Y.,Lu, W.,Jones, R.B.,Linhardt, R.J.,Capila, I.,Toida, T.,Kan, M.,Pelletier, H.,McKeehan, W.L.
Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.
Biochemistry, 40:14429-14439, 2001

PubMed Abstract: Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.

PubMed: 11724555
DOI: 10.1021/bi011000u

Experimental method

X-RAY DIFFRACTION (2.3 Å)