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dc.contributor.authorBrown, Aen_GB
dc.contributor.authorRobinson, Christopher Jen_GB
dc.contributor.authorGallagher, John Ten_GB
dc.contributor.authorBlundell, Ten_GB
dc.date.accessioned2013-06-28T15:53:40Z
dc.date.available2013-06-28T15:53:40Z
dc.date.issued2013-04-16
dc.identifier.citationCooperative heparin-mediated oligomerization of fibroblast growth factor-1 (FGF1) precedes recruitment of FGFR2 to ternary complexes. 2013, 104 (8):1720-30 Biophys Jen_GB
dc.identifier.issn1542-0086
dc.identifier.pmid23601319
dc.identifier.doi10.1016/j.bpj.2013.02.051
dc.identifier.urihttp://hdl.handle.net/10541/294892
dc.description.abstractFibroblast growth factors (FGFs) utilize cell surface heparan sulfate as a coreceptor in the assembly of signaling complexes with FGF-receptors on the plasma membrane. Here we undertake a complete thermodynamic characterization of the assembly of the FGF signaling complex using isothermal titration calorimetry. Heparin fragments of defined length are used as chemical analogs of the sulfated domains of heparan sulfate and examined for their ability to oligomerize FGF1. Binding is modeled using the McGhee-von Hippel formalism for the cooperative binding of ligands to a monodimensional lattice. Oligomerization of FGFs on heparin is shown to be mediated by positive cooperativity (α = 6). Heparin octasaccharide is the shortest length capable of dimerizing FGF1 and on longer heparin chains FGF1 binds with a minimal footprint of 4.2 saccharide units. The thermodynamics and stoichiometry of the ternary complex suggest that in solution FGF1 binds to heparin in a trans-dimeric manner before FGFR recruitment.
dc.language.isoenen
dc.rightsArchived with thanks to Biophysical journalen_GB
dc.titleCooperative heparin-mediated oligomerization of fibroblast growth factor-1 (FGF1) precedes recruitment of FGFR2 to ternary complexes.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, University of Cambridge, Cambridge, United Kingdom. ab604@cam.ac.uken_GB
dc.identifier.journalBiophysical Journalen_GB
html.description.abstractFibroblast growth factors (FGFs) utilize cell surface heparan sulfate as a coreceptor in the assembly of signaling complexes with FGF-receptors on the plasma membrane. Here we undertake a complete thermodynamic characterization of the assembly of the FGF signaling complex using isothermal titration calorimetry. Heparin fragments of defined length are used as chemical analogs of the sulfated domains of heparan sulfate and examined for their ability to oligomerize FGF1. Binding is modeled using the McGhee-von Hippel formalism for the cooperative binding of ligands to a monodimensional lattice. Oligomerization of FGFs on heparin is shown to be mediated by positive cooperativity (α = 6). Heparin octasaccharide is the shortest length capable of dimerizing FGF1 and on longer heparin chains FGF1 binds with a minimal footprint of 4.2 saccharide units. The thermodynamics and stoichiometry of the ternary complex suggest that in solution FGF1 binds to heparin in a trans-dimeric manner before FGFR recruitment.


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