1axm: Difference between revisions
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==Overview== | ==Overview== | ||
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. | 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== | |||
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]], LADD syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602115 602115]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: human acidic fibroblast growth factor]] | [[Category: human acidic fibroblast growth factor]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:03:34 2007'' | ||
Revision as of 16:57, 12 November 2007
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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. Structure known Active Sites: HPA, HPB, HPC, HPD, HPE and HPF. 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
Page seeded by OCA on Mon Nov 12 16:03:34 2007