1E0O

CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX

Summary for 1E0O

• Entry DOI: 10.2210/pdb1e0o/pdb
• Related: 1AXM 1CVS 1DJS 2AXM
• Descriptor: FIBROBLAST GROWTH FACTOR 1, FIBROBLAST GROWTH FACTOR RECEPTOR 2, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: growth factor, receptor tyrosine kinase, heparin, ternary complex, signal transduction
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 84448.54

Authors

Pellegrini, L.,Burke, D.F.,von Delft, F.,Mulloy, B.,Blundell, T.L. (deposition date: 2000-04-03, release date: 2000-10-23, Last modification date: 2024-11-06)

Primary citation

Pellegrini, L.,Burke, D.F.,von Delft, F.,Mulloy, B.,Blundell, T.L.
Crystal Structure of Fibroblast Growth Factor Receptor Ectodomain Bound to Ligand and Heparin
Nature, 407:1029-, 2000

PubMed Abstract: Fibroblast growth factors (FGFs) are a large family of structurally related proteins with a wide range of physiological and pathological activities. Signal transduction requires association of FGF with its receptor tyrosine kinase (FGFR) and heparan sulphate proteoglycan in a specific complex on the cell surface. Direct involvement of the heparan sulphate glycosaminoglycan polysaccharide in the molecular association between FGF and its receptor is essential for biological activity. Although crystal structures of binary complexes of FGF-heparin and FGF-FGFR have been described, the molecular architecture of the FGF signalling complex has not been elucidated. Here we report the crystal structure of the FGFR2 ectodomain in a dimeric form that is induced by simultaneous binding to FGF1 and a heparin decasaccharide. The complex is assembled around a central heparin molecule linking two FGF1 ligands into a dimer that bridges between two receptor chains. The asymmetric heparin binding involves contacts with both FGF1 molecules but only one receptor chain. The structure of the FGF1-FGFR2-heparin ternary complex provides a structural basis for the essential role of heparan sulphate in FGF signalling.

PubMed: 11069186
DOI: 10.1038/35039551

Experimental method

X-RAY DIFFRACTION (2.8 Å)