6m6e
From Proteopedia
(Difference between revisions)
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==Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)== | ==Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)== | ||
| - | <StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]]' scene=''> | + | <StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>[[6m6e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M6E FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF21 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6m6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m6e OCA], [https://pdbe.org/6m6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m6e RCSB], [https://www.ebi.ac.uk/pdbsum/6m6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m6e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/FGF21_HUMAN FGF21_HUMAN]] Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB.<ref>PMID:15902306</ref> <ref>PMID:17623664</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fibroblast growth factor 21 (FGF21) is a regulator of glucose and lipid metabolism. It has been widely considered as a promising candidate for the treatment of type 2 diabetes mellitus (T2DM) and other related metabolic disorders. However, lack of structural and dynamic information has limited FGF21-based drug development. Here, using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of FGF21 and find that its non-canonical flexible beta-trefoil conformation affects the folding of beta2-beta3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21-FGF19 chimera, FGF21(SS) . As expected, FGF21(SS) shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21(SS) shows its better insulin sensitivity, reduced inflammation in 3T3-L1 adipocytes, and lower blood glucose and insulin levels in ob/ob mice compared with wild type. Our dynamics-based rational design provides a promising approach for FGF21-based therapeutic development against T2DM. | ||
| + | |||
| + | Dynamic folding modulation generates FGF21 variant against diabetes.,Zhu L, Zhao H, Liu J, Cai H, Wu B, Liu Z, Zhou S, Liu Q, Li X, Bao B, Liu J, Dai H, Wang J EMBO Rep. 2020 Dec 9:e51352. doi: 10.15252/embr.202051352. PMID:33295692<ref>PMID:33295692</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m6e" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Wang J]] | + | [[Category: Wang, J]] |
| - | [[Category: Zhao H]] | + | [[Category: Zhao, H]] |
| - | [[Category: Zhu L]] | + | [[Category: Zhu, L]] |
| + | [[Category: Anti-diabete]] | ||
| + | [[Category: Beta-klotho binding]] | ||
| + | [[Category: Beta-trefoil conformation]] | ||
| + | [[Category: Hormone]] | ||
| + | [[Category: Metabolic regulator]] | ||
Revision as of 14:54, 3 March 2021
Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)
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