Structural basis for FGF receptor dimerization and activation

Cell. 1999 Sep 3;98(5):641-50. doi: 10.1016/s0092-8674(00)80051-3.


The crystal structure of FGF2 bound to a naturally occurring variant of FGF receptor 1 (FGFR1) consisting of immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 A resolution. Two FGF2:FGFR1 complexes form a 2-fold symmetric dimer. Within each complex, FGF2 interacts extensively with D2 and D3 as well as with the linker between the two domains. The dimer is stabilized by interactions between FGF2 and D2 of the adjoining complex and by a direct interaction between D2 of each receptor. A positively charged canyon formed by a cluster of exposed basic residues likely represents the heparin-binding site. A general model for FGF- and heparin-induced FGFR dimerization is inferred from the crystal structure, unifying a wealth of biochemical data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Dimerization
  • Fibroblast Growth Factor 2 / chemistry
  • Heparin / chemistry
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Myosin-Light-Chain Kinase
  • Peptide Fragments
  • Peptides
  • Protein Structure, Tertiary
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptors, Fibroblast Growth Factor / chemistry*
  • Receptors, Fibroblast Growth Factor / physiology*
  • Sequence Homology, Amino Acid


  • Ligands
  • Muscle Proteins
  • Peptide Fragments
  • Peptides
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • telokin
  • Heparin
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Fibroblast Growth Factor, Type 1
  • Myosin-Light-Chain Kinase

Associated data

  • PDB/1CVS