Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization

Mol Cell. 2000 Sep;6(3):743-50. doi: 10.1016/s1097-2765(00)00073-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography
  • Dimerization
  • Fibroblast Growth Factors / chemistry*
  • Fibroblast Growth Factors / metabolism
  • Heparin / chemistry*
  • Heparin / metabolism
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Receptors, Fibroblast Growth Factor / chemistry*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Sulfates / chemistry
  • Sulfates / metabolism


  • Receptors, Fibroblast Growth Factor
  • Sulfates
  • Fibroblast Growth Factors
  • Heparin

Associated data

  • PDB/1FQ9