2p39: Difference between revisions
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New page: left|200px<br /> <applet load="2p39" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p39, resolution 1.5Å" /> '''Crystal structure of... |
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[[Image:2p39.gif|left|200px]]<br /> | [[Image:2p39.gif|left|200px]]<br /><applet load="2p39" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2p39" size=" | |||
caption="2p39, resolution 1.5Å" /> | caption="2p39, resolution 1.5Å" /> | ||
'''Crystal structure of human FGF23'''<br /> | '''Crystal structure of human FGF23'''<br /> | ||
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==Overview== | ==Overview== | ||
Unique among FGFs, fibroblast growth factor (FGF)-19, FGF21 and FGF23 act, in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of, klotho/betaklotho in their target tissues. Here, we present the crystal, structures of FGF19 alone and of FGF23 in complex with sucrose, octasulfate, a disaccharide chemically related to heparin. The, conformation of the heparin-binding region between beta strands 10 and 12, in FGF19 and FGF23 diverges completely from the common conformation, adopted by paracrine-acting FGFs. A cleft between this region and the, beta1-beta2 loop, the other heparin-binding region, precludes direct, interaction between heparin/heparan sulfate and backbone atoms of, FGF19/23. This reduces the heparin-binding affinity of these ligands and, confers endocrine function. Klotho/betaklotho have evolved as a, compensatory mechanism for the poor ability of heparin/heparan sulfate to, promote binding of FGF19/21/23 to their cognate receptors. | Unique among FGFs, fibroblast growth factor (FGF)-19, FGF21 and FGF23 act, in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of, klotho/betaklotho in their target tissues. Here, we present the crystal, structures of FGF19 alone and of FGF23 in complex with sucrose, octasulfate, a disaccharide chemically related to heparin. The, conformation of the heparin-binding region between beta strands 10 and 12, in FGF19 and FGF23 diverges completely from the common conformation, adopted by paracrine-acting FGFs. A cleft between this region and the, beta1-beta2 loop, the other heparin-binding region, precludes direct, interaction between heparin/heparan sulfate and backbone atoms of, FGF19/23. This reduces the heparin-binding affinity of these ligands and, confers endocrine function. Klotho/betaklotho have evolved as a, compensatory mechanism for the poor ability of heparin/heparan sulfate to, promote binding of FGF19/21/23 to their cognate receptors. | ||
==About this Structure== | ==About this Structure== | ||
2P39 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SCR as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2P39 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SCR:'>SCR</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P39 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: atypical beta-trefoil fold]] | [[Category: atypical beta-trefoil fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:33:00 2008'' | ||
