1qqk
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1qql|1QQL]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1qqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qqk OCA], [http://www.ebi.ac.uk/pdbsum/1qqk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1qqk RCSB]</span> | ||
}} | }} | ||
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[[Category: beta-trefoil]] | [[Category: beta-trefoil]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:17:35 2008'' |
Revision as of 20:17, 30 March 2008
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| , resolution 3.1Å | |||||||
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| Related: | 1QQL
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE CRYSTAL STRUCTURE OF FIBROBLAST GROWTH FACTOR 7 (KERATINOCYTE GROWTH FACTOR)
Overview
Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.
About this Structure
1QQK is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs., Ye S, Luo Y, Lu W, Jones RB, Linhardt RJ, Capila I, Toida T, Kan M, Pelletier H, McKeehan WL, Biochemistry. 2001 Dec 4;40(48):14429-39. PMID:11724555
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