A new dimeric structure of FGFR D2 domain may contribute to the FGF signaling pathway
by Guo, Fei; Dakshinamurthy, Rajalingam; Kumar, Thallapuranam Krishnaswamy Suresh; Sakon, Josh
Fibroblast groth factors (FGFs) regulate many crucial biol. functions including cell proliferation, differentiation, and angiogenesis. The FGF signaling pathway is activated by Four (Ig)-like receptors (FGFR1-4). FGFRs consist of three extracellular ligand binding domains (D1,D2,D3), a single transmembrane helix, and cytoplasmic tyrosine kinase domain. Cell surface-bound HSPGs supported dimerization of the FGFRs are required to activate the signaling pathway. The D2 domain is suggested to bind with both HSPGs and FGFs to form a ternary complex. We solved the crystal structures of the D2 domain of the FGFR2, and the D2-sucrose octasulfate (SOS) complex by X-ray crystallog. The D2 domain formed a crystallog. 2-fold symmetry dimer which is different from other crystallog. studies of FGFRs. But the SOS binding sites showed consistant residues with them. This new dimer structure is more easier to explain the signal transduction mechanism by introducing orientation changes of the receptors rather than conformational changes.