1FQ9

CRYSTAL STRUCTURE OF A TERNARY FGF2-FGFR1-HEPARIN COMPLEX

Summary for 1FQ9

• Entry DOI: 10.2210/pdb1fq9/pdb
• Related: 1CVS
• Descriptor: FIBROBLAST GROWTH FACTOR 2, FIBROBLAST GROWTH FACTOR RECEPTOR 1, 4-deoxy-2-O-sulfo-alpha-L-threo-hex-4-enopyranuronic 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-beta-L-altropyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: i-set subgroup within the immunoglobulin superfamily, b-trefoil fold, growth factor-growth factor receptor complex, growth factor/growth factor receptor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 84812.58

Authors

Schlessinger, J.,Plotnikov, A.N.,Ibrahimi, O.A.,Eliseenkova, A.V.,Yeh, B.K.,Yayon, A.,Linhardt, R.J.,Mohammadi, M. (deposition date: 2000-09-04, release date: 2000-09-27, Last modification date: 2024-10-30)

Primary citation

Schlessinger, J.,Plotnikov, A.N.,Ibrahimi, O.A.,Eliseenkova, A.V.,Yeh, B.K.,Yayon, A.,Linhardt, R.J.,Mohammadi, M.
Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.
Mol.Cell, 6:743-750, 2000

PubMed Abstract: The crystal structure of a dimeric 2:2:2 FGF:FGFR:heparin ternary complex at 3 A resolution has been determined. Within each 1:1 FGF:FGFR complex, heparin makes numerous contacts with both FGF and FGFR, thereby augmenting FGF-FGFR binding. Heparin also interacts with FGFR in the adjoining 1:1 FGF:FGFR complex to promote FGFR dimerization. The 6-O-sulfate group of heparin plays a pivotal role in mediating both interactions. The unexpected stoichiometry of heparin binding in the structure led us to propose a revised model for FGFR dimerization. Biochemical data in support of this model are also presented. This model provides a structural basis for FGFR activation by small molecule heparin analogs and may facilitate the design of heparin mimetics capable of modulating FGF signaling.

PubMed: 11030354
DOI: 10.1016/S1097-2765(00)00073-3

Experimental method

X-RAY DIFFRACTION (3 Å)