TI  - Crystal structure of fibroblast growth factor receptor ectodomain bound to
      ligand and heparin.
PG  - 1029-34
AB  - 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  <prot>FGFR2</prot>  ectodomain in a dimeric form that is induced by
      simultaneous binding to  <prot>FGF1</prot>  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  <prot>FGF1</prot> - <prot>FGFR2</prot> - heparin  ternary complex provides a
      structural basis for the essential role of heparan sulphate in FGF
      signalling.
AD  - Department of Biochemistry, University of Cambridge, UK.
