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6m6e

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Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)

Structural highlights

6m6e is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005 Jun;115(6):1627-35. doi: 10.1172/JCI23606. Epub 2005 May 2. PMID:15902306 doi:http://dx.doi.org/10.1172/JCI23606
↑ Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-95. Epub 2007 Jul 10. PMID:17623664 doi:10.1074/jbc.M704165200
↑ 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. Dynamic folding modulation generates FGF21 variant against diabetes. EMBO Rep. 2020 Dec 9:e51352. doi: 10.15252/embr.202051352. PMID:33295692 doi:http://dx.doi.org/10.15252/embr.202051352

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6m6e"

Categories: Homo sapiens | Large Structures | Wang J | Zhao H | Zhu L

@@ Line 1: / Line 1: @@
 ==Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)==
-<StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='6m6e' size='340' side='right'caption='[[6m6e]]' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[6m6e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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='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>
+</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>
-<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>
 == 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>
+[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 ==
@@ Line 18: / Line 17: @@
 </div>
 <div class="pdbe-citations 6m6e" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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]]

6m6e

From Proteopedia

Current revision

Solution structure of the core domain of Fibroblast growth factor 21 (FGF21)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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