View source for 5w21


==Crystal Structure of a 1:1:1 FGF23-FGFR1c-aKlotho Ternary Complex==
<StructureSection load='5w21' size='340' side='right'caption='[[5w21]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5w21]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W21 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5w21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w21 OCA], [https://pdbe.org/5w21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w21 RCSB], [https://www.ebi.ac.uk/pdbsum/5w21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w21 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KLOT_HUMAN KLOT_HUMAN] Familial tumoral calcinosis. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/KLOT_HUMAN KLOT_HUMAN] May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).  The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ageing suppressor alpha-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of alpha-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, alpha-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of alpha-klotho is incompatible with its purported glycosidase activity. Thus, shed alpha-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.

alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.,Chen G, Liu Y, Goetz R, Fu L, Jayaraman S, Hu MC, Moe OW, Liang G, Li X, Mohammadi M Nature. 2018 Jan 25;553(7689):461-466. doi: 10.1038/nature25451. Epub 2018 Jan, 17. PMID:29342138<ref>PMID:29342138</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5w21" style="background-color:#fffaf0;"></div>

==See Also==
*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
*[[Fibroblast growth factor receptor 3D receptor|Fibroblast growth factor receptor 3D receptor]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mohammadi M]]