1axm: Difference between revisions
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==Overview== | ==Overview== | ||
The fibroblast growth factors (FGFs) form a large family of structurally | The fibroblast growth factors (FGFs) form a large family of structurally related, multifunctional proteins that regulate various biological responses. They mediate cellular functions by binding to transmembrane FGF receptors, which are protein tyrosine kinases. FGF receptors are activated by oligomerization, and both this activation and FGF-stimulated biological responses require heparin-like molecules as well as FGF. Heparins are linear anionic polysaccharide chains; they are typically heterogeneously sulphated on alternating L-iduronic and D-glucosamino sugars, and are nearly ubiquitous in animal tissues as heparan sulphate proteoglycans on cell surfaces and in the extracellular matrix. Although several crystal structures have been described for FGF molecules in complexes with heparin-like sugars, the nature of a biologically active complex has been unknown until now. Here we describe the X-ray crystal structure, at 2.9 A resolution, of a biologically active dimer of human acidic FGF in a complex with a fully sulphated, homogeneous heparin decassacharide. The dimerization of heparin-linked acidic FGF observed here is an elegant mechanism for the modulation of signalling through combinatorial homodimerization and heterodimerization of the 12 known members of the FGF family. | ||
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chen, D | [[Category: Chen, D I.]] | ||
[[Category: DiGabriele, A | [[Category: DiGabriele, A D.]] | ||
[[Category: Hendrickson, W | [[Category: Hendrickson, W A.]] | ||
[[Category: Jaye, M.]] | [[Category: Jaye, M.]] | ||
[[Category: Lax, I.]] | [[Category: Lax, I.]] | ||
[[Category: Schlessinger, J.]] | [[Category: Schlessinger, J.]] | ||
[[Category: Svahn, C | [[Category: Svahn, C M.]] | ||
[[Category: heparin decasaccharide]] | [[Category: heparin decasaccharide]] | ||
[[Category: human acidic fibroblast growth factor]] | [[Category: human acidic fibroblast growth factor]] | ||
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Revision as of 12:49, 21 February 2008
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HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR
OverviewOverview
The fibroblast growth factors (FGFs) form a large family of structurally related, multifunctional proteins that regulate various biological responses. They mediate cellular functions by binding to transmembrane FGF receptors, which are protein tyrosine kinases. FGF receptors are activated by oligomerization, and both this activation and FGF-stimulated biological responses require heparin-like molecules as well as FGF. Heparins are linear anionic polysaccharide chains; they are typically heterogeneously sulphated on alternating L-iduronic and D-glucosamino sugars, and are nearly ubiquitous in animal tissues as heparan sulphate proteoglycans on cell surfaces and in the extracellular matrix. Although several crystal structures have been described for FGF molecules in complexes with heparin-like sugars, the nature of a biologically active complex has been unknown until now. Here we describe the X-ray crystal structure, at 2.9 A resolution, of a biologically active dimer of human acidic FGF in a complex with a fully sulphated, homogeneous heparin decassacharide. The dimerization of heparin-linked acidic FGF observed here is an elegant mechanism for the modulation of signalling through combinatorial homodimerization and heterodimerization of the 12 known members of the FGF family.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
1AXM is a Single protein structure of sequence from Homo sapiens. Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.
ReferenceReference
Structure of a heparin-linked biologically active dimer of fibroblast growth factor., DiGabriele AD, Lax I, Chen DI, Svahn CM, Jaye M, Schlessinger J, Hendrickson WA, Nature. 1998 Jun 25;393(6687):812-7. PMID:9655399
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