2P39

Crystal structure of human FGF23

Summary for 2P39

• Entry DOI: 10.2210/pdb2p39/pdb
• Related: 2P23
• Related PRD ID: PRD_900013
• Descriptor: Fibroblast growth factor 23, 1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose-(2-1)-2,3,4,6-tetra-O-sulfonato-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: atypical beta-trefoil fold, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 18839.04

Authors

Mohammadi, M. (deposition date: 2007-03-08, release date: 2007-04-10, Last modification date: 2024-10-30)

Primary citation

Goetz, R.,Beenken, A.,Ibrahimi, O.A.,Kalinina, J.,Olsen, S.K.,Eliseenkova, A.V.,Xu, C.,Neubert, T.A.,Zhang, F.,Linhardt, R.J.,Yu, X.,White, K.E.,Inagaki, T.,Kliewer, S.A.,Yamamoto, M.,Kurosu, H.,Ogawa, Y.,Kuro-O, M.,Lanske, B.,Razzaque, M.S.,Mohammadi, M.
Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members.
Mol.Cell.Biol., 27:3417-3428, 2007

PubMed Abstract: 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.

PubMed: 17339340
DOI: 10.1128/MCB.02249-06

Experimental method

X-RAY DIFFRACTION (1.5 Å)