5w59 | pdb_00005w59

Crystal structure of a monomeric human FGF9 in complex with the ectodomain of human FGFR1c

spinqualitylabelsall models 5w59, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w59 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.498Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FGF9_HUMAN Defects in FGF9 are the cause of multiple synostoses syndrome type 3 (SYNS3) [MIM:612961. Multiple synostoses syndrome is an autosomal dominant condition characterized by progressive joint fusions of the fingers, wrists, ankles and cervical spine, characteristic facies and progressive conductive deafness. Function FGF9_HUMAN Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. Publication Abstract from PubMed The epithelial fibroblast growth factor 9 (FGF9) subfamily specifically binds and activates the mesenchymal "c" splice isoform of FGF receptors 1-3 (FGFR1-3) to regulate organogenesis and tissue homeostasis. The unique N and C termini of FGF9 subfamily ligands mediate a reversible homodimerization that occludes major receptor binding sites within the ligand core region. Here we provide compelling X-ray crystallographic, biophysical, and biochemical data showing that homodimerization controls receptor binding specificity of the FGF9 subfamily by keeping the concentration of active FGF9 monomers at a level, which is sufficient for a normal FGFR "c" isoform binding/signaling, but is insufficient for an illegitimate FGFR "b" isoform binding/signaling. We show that deletion of the N terminus or alanine substitutions in the C terminus of FGF9 skews the delicate ligand equilibrium toward active FGF9 monomers causing off-target binding and activation of FGFR b isoforms. Our study is the first to implicate ligand homodimerization in the regulation of ligand-receptor specificity. Regulation of Receptor Binding Specificity of FGF9 by an Autoinhibitory Homodimerization.,Liu Y, Ma J, Beenken A, Srinivasan L, Eliseenkova AV, Mohammadi M Structure. 2017 Jul 11. pii: S0969-2126(17)30212-5. doi:, 10.1016/j.str.2017.06.016. PMID:28757146 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fibroblast growth factor 3D structures Fibroblast growth factor receptor 3D receptor

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