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[[Image:1axm.gif|left|200px]]<br /><applet load="1axm" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1axm, resolution 3.00&Aring;" />
'''HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR'''<br />


==Overview==
==HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR==
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.
<StructureSection load='1axm' size='340' side='right'caption='[[1axm]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1axm]] is a 6 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=1AXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AXM 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]] 3&#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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</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=1axm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1axm OCA], [https://pdbe.org/1axm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1axm RCSB], [https://www.ebi.ac.uk/pdbsum/1axm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1axm 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/ax/1axm_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1axm ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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==
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<ref>PMID:9655399</ref>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1AXM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Known structural/functional Sites: <scene name='pdbsite=HPA:Heparin Binding Loop'>HPA</scene>, <scene name='pdbsite=HPB:Heparin Binding Loop'>HPB</scene>, <scene name='pdbsite=HPC:Heparin Binding Loop'>HPC</scene>, <scene name='pdbsite=HPD:Heparin Binding Loop'>HPD</scene>, <scene name='pdbsite=HPE:Heparin Binding Loop'>HPE</scene> and <scene name='pdbsite=HPF:Heparin Binding Loop'>HPF</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AXM OCA].
</div>
<div class="pdbe-citations 1axm" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9655399 9655399]
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chen, D.I.]]
[[Category: Chen DI]]
[[Category: DiGabriele, A.D.]]
[[Category: DiGabriele AD]]
[[Category: Hendrickson, W.A.]]
[[Category: Hendrickson WA]]
[[Category: Jaye, M.]]
[[Category: Jaye M]]
[[Category: Lax, I.]]
[[Category: Lax I]]
[[Category: Schlessinger, J.]]
[[Category: Schlessinger J]]
[[Category: Svahn, C.M.]]
[[Category: Svahn CM]]
[[Category: heparin decasaccharide]]
[[Category: human acidic fibroblast growth factor]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Dec 19 13:19:30 2007''

Latest revision as of 10:16, 23 October 2024

HEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTORHEPARIN-LINKED BIOLOGICALLY-ACTIVE DIMER OF FIBROBLAST GROWTH FACTOR

Structural highlights

1axm is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. PMID:8663044
  2. ↑ Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. PMID:16597617 doi:10.1074/jbc.M601252200
  3. ↑ Fernandez IS, Cuevas P, Angulo J, Lopez-Navajas P, Canales-Mayordomo A, Gonzalez-Corrochano R, Lozano RM, Valverde S, Jimenez-Barbero J, Romero A, Gimenez-Gallego G. Gentisic acid, a compound associated with plant defense and a metabolite of aspirin, heads a new class of in vivo fibroblast growth factor inhibitors. J Biol Chem. 2010 Apr 9;285(15):11714-29. Epub 2010 Feb 9. PMID:20145243 doi:10.1074/jbc.M109.064618
  4. ↑ DiGabriele AD, Lax I, Chen DI, Svahn CM, Jaye M, Schlessinger J, Hendrickson WA. Structure of a heparin-linked biologically active dimer of fibroblast growth factor. Nature. 1998 Jun 25;393(6687):812-7. PMID:9655399 doi:10.1038/31741

1axm, resolution 3.00Å

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