1axm: Difference between revisions

No edit summary
No edit summary
Line 4: Line 4:
|PDB= 1axm |SIZE=350|CAPTION= <scene name='initialview01'>1axm</scene>, resolution 3.00&Aring;
|PDB= 1axm |SIZE=350|CAPTION= <scene name='initialview01'>1axm</scene>, resolution 3.00&Aring;
|SITE= <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>
|SITE= <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>
|LIGAND=  
|LIGAND= <scene name='pdbligand=IDS:O2-SULFO-GLUCURONIC+ACID'>IDS</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene>
|ACTIVITY=  
|ACTIVITY=  
|GENE= ECGF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|GENE= ECGF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
|DOMAIN=
|RELATEDENTRY=
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1axm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1axm OCA], [http://www.ebi.ac.uk/pdbsum/1axm PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1axm RCSB]</span>
}}
}}


Line 14: Line 17:
==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==
Line 35: Line 35:
[[Category: human acidic fibroblast growth factor]]
[[Category: human acidic fibroblast growth factor]]


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:03:32 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:49:28 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA