title: Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity.
abstract: To elucidate the structural determinants governing specificity in fibroblast growth factor (FGF) signaling, we have determined the crystal structures of FGF1 and FGF2 complexed with the ligand binding domains (immunoglobulin-like domains 2 [D2] and 3 [D3]) of FGF receptor 1 (FGFR1) and FGFR2, respectively. Highly conserved FGF-D2 and FGF-linker (between D2-D3) interfaces define a general binding site for all FGF-FGFR complexes. Specificity is achieved through interactions between the N-terminal and central regions of FGFs and two loop regions in D3 that are subject to alternative splicing. These structures provide a molecular basis for FGF1 as a universal FGFR ligand and for modulation of FGF-FGFR specificity through primary sequence variations and alternative splicing.
authors.affiliation: Department of Pharmacology, New York University School of Medicine, New York 10016, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Plotnikov
authors.forename: S R
authors.initials: SR
authors.lastname: Hubbard
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: M
authors.initials: M
authors.lastname: Mohammadi
mesh_terms: D000595:Amino Acid Sequence; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1