2p23: Difference between revisions

Revision as of 19:25, 21 February 2008

Crystal structure of human FGF19

OverviewOverview

Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 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 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, and -23 to their cognate receptors.

About this StructureAbout this Structure

2P23 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members., Goetz R, Beenken A, Ibrahimi OA, Kalinina J, Olsen SK, Eliseenkova AV, Xu C, Neubert TA, Zhang F, Linhardt RJ, Yu X, White KE, Inagaki T, Kliewer SA, Yamamoto M, Kurosu H, Ogawa Y, Kuro-o M, Lanske B, Razzaque MS, Mohammadi M, Mol Cell Biol. 2007 May;27(9):3417-28. Epub 2007 Mar 5. PMID:17339340

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OCA

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 ==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 fibroblast growth factors (FGFs), FGF19, -21, and -23 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 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, and -23 to their cognate receptors.
 ==About this Structure==
@@ Line 10: / Line 10: @@
 ==Reference==
-Molecular Insights into the Klotho-Dependent, Endocrine Mode of Action of FGF19 Subfamily Members., Goetz R, Beenken A, Ibrahimi OA, Kalinina J, Olsen SK, Eliseenkova AV, Xu C, Neubert T, Zhang F, Linhardt RJ, Yu X, White KE, Inagaki T, Kliewer SA, Yamamoto M, Kurosu H, Ogawa Y, Kuro-O M, Lanske B, Razzaque MS, Mohammadi M, Mol Cell Biol. 2007 Mar 5;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17339340 17339340]
+Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members., Goetz R, Beenken A, Ibrahimi OA, Kalinina J, Olsen SK, Eliseenkova AV, Xu C, Neubert TA, Zhang F, Linhardt RJ, Yu X, White KE, Inagaki T, Kliewer SA, Yamamoto M, Kurosu H, Ogawa Y, Kuro-o M, Lanske B, Razzaque MS, Mohammadi M, Mol Cell Biol. 2007 May;27(9):3417-28. Epub 2007 Mar 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17339340 17339340]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
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 [[Category: atypical beta-trefoil fold]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:32:59 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:25:00 2008''