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1e0o

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CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX

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-[[Image:1e0o.gif|left|200px]]<br />
-<applet load="1e0o" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1e0o, resolution 2.80&Aring;" />
-'''CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX'''<br />
-==Overview==
+==CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX==
-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.
+<StructureSection load='1e0o' size='340' side='right'caption='[[1e0o]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1e0o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E0O FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1e0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e0o OCA], [https://pdbe.org/1e0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e0o RCSB], [https://www.ebi.ac.uk/pdbsum/1e0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e0o ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_HUMAN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e0/1e0o_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1e0o ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-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]]
+*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
+*[[Fibroblast growth factor receptor 3D receptor|Fibroblast growth factor receptor 3D receptor]]
-==About this Structure==
+== References ==
-E0O 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1E0O OCA].
+<references/>
+__TOC__
-==Reference==
+</StructureSection>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11069186 11069186]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Blundell, T.L.]]
+[[Category: Blundell TL]]
-[[Category: Burke, D.F.]]
+[[Category: Burke DF]]
-[[Category: Delft, F.Von.]]
+[[Category: Mulloy B]]
-[[Category: Mulloy, B.]]
+[[Category: Pellegrini L]]
-[[Category: Pellegrini, L.]]
+[[Category: Von Delft F]]
-[[Category: NI]]
-[[Category: SO4]]
-[[Category: growth factor]]
-[[Category: heparin]]
-[[Category: receptor tyrosine kinase]]
-[[Category: signal transduction]]
-[[Category: ternary complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:38:12 2007''

1e0o

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CRYSTAL STRUCTURE OF A TERNARY FGF1-FGFR2-HEPARIN COMPLEX

Structural highlights

Function

Evolutionary Conservation

See Also

References

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