Structural basis for FGF receptor dimerization and activation

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 Angstrom resolution. Two FGF2:FGFR1 complex es form a 2-fold symmetric dimer. Within each complex, FGF2 interacts exten sively with D2 and D3 as well as with the linker between the two domains. T he dimer is stabilized by interactions between FGF2 and D2 of the adjoining complex and by a direct interaction between D2 of each receptor. A positiv ely charged canyon formed by a cluster of exposed basic residues likely rep resents the heparin-binding site. A general model for FGF- and heparin-indu ced FGFR dimerization is inferred from the crystal structure, unifying a we alth of biochemical data.