1e0o
From Proteopedia
(New page: 200px<br /> <applet load="1e0o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1e0o, resolution 2.80Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1e0o.gif|left|200px]]<br /> | + | [[Image:1e0o.gif|left|200px]]<br /><applet load="1e0o" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1e0o" size=" | + | |
caption="1e0o, resolution 2.80Å" /> | caption="1e0o, resolution 2.80Å" /> | ||
'''CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX'''<br /> | '''CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fibroblast growth factors (FGFs) are a large family of structurally | + | Fibroblast growth factors (FGFs) are a large family of structurally related proteins with a wide range of physiological and pathological activities. Signal transduction requires association of FGF with its receptor tyrosine kinase (FGFR) and heparan sulphate proteoglycan in a specific complex on the cell surface. Direct involvement of the heparan sulphate glycosaminoglycan polysaccharide in the molecular association between FGF and its receptor is essential for biological activity. Although crystal structures of binary complexes of FGF-heparin and FGF-FGFR have been described, the molecular architecture of the FGF signalling complex has not been elucidated. Here we report the crystal structure of the FGFR2 ectodomain in a dimeric form that is induced by simultaneous binding to FGF1 and a heparin decasaccharide. The complex is assembled around a central heparin molecule linking two FGF1 ligands into a dimer that bridges between two receptor chains. The asymmetric heparin binding involves contacts with both FGF1 molecules but only one receptor chain. The structure of the FGF1-FGFR2-heparin ternary complex provides a structural basis for the essential role of heparan sulphate in FGF signalling. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1E0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NI and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1E0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NI:'>NI</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0O OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Blundell, T | + | [[Category: Blundell, T L.]] |
| - | [[Category: Burke, D | + | [[Category: Burke, D F.]] |
| - | [[Category: Delft, F | + | [[Category: Delft, F Von.]] |
[[Category: Mulloy, B.]] | [[Category: Mulloy, B.]] | ||
[[Category: Pellegrini, L.]] | [[Category: Pellegrini, L.]] | ||
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[[Category: ternary complex]] | [[Category: ternary complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:22:37 2008'' |
Revision as of 10:22, 21 February 2008
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CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX
Contents |
Overview
Fibroblast growth factors (FGFs) are a large family of structurally related proteins with a wide range of physiological and pathological activities. Signal transduction requires association of FGF with its receptor tyrosine kinase (FGFR) and heparan sulphate proteoglycan in a specific complex on the cell surface. Direct involvement of the heparan sulphate glycosaminoglycan polysaccharide in the molecular association between FGF and its receptor is essential for biological activity. Although crystal structures of binary complexes of FGF-heparin and FGF-FGFR have been described, the molecular architecture of the FGF signalling complex has not been elucidated. Here we report the crystal structure of the FGFR2 ectodomain in a dimeric form that is induced by simultaneous binding to FGF1 and a heparin decasaccharide. The complex is assembled around a central heparin molecule linking two FGF1 ligands into a dimer that bridges between two receptor chains. The asymmetric heparin binding involves contacts with both FGF1 molecules but only one receptor chain. The structure of the FGF1-FGFR2-heparin ternary complex provides a structural basis for the essential role of heparan sulphate in FGF signalling.
Disease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this Structure
1E0O is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin., Pellegrini L, Burke DF, von Delft F, Mulloy B, Blundell TL, Nature. 2000 Oct 26;407(6807):1029-34. PMID:11069186
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