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1osv

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Revision as of 09:21, 8 September 2021

STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR

Structural highlights

1osv is a 5 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NR1H4_RAT] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) and activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 within its gene locus (By similarity). [NCOA2_MOUSE] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The nuclear receptor FXR is the sensor of physiological levels of enterohepatic bile acids, the end products of cholesterol catabolism. Here we report crystal structures of the FXR ligand binding domain in complex with coactivator peptide and two different bile acids. An unusual A/B ring juncture, a feature associated with bile acids and no other steroids, provides ligand discrimination and triggers a pi-cation switch that activates FXR. Helix 12, the activation function 2 of the receptor, adopts the agonist conformation and stabilizes coactivator peptide binding. FXR is able to interact simultaneously with two coactivator motifs, providing a mechanism for enhanced binding of coactivators through intermolecular contacts between their LXXLL sequences. These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis.

Structural basis for bile acid binding and activation of the nuclear receptor FXR.,Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F Mol Cell. 2003 Apr;11(4):1093-100. PMID:12718893^[3]

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

References

↑ Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW, Chambon P, Auwerx J. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002 Dec 27;111(7):931-41. PMID:12507421
↑ Lee YH, Koh SS, Zhang X, Cheng X, Stallcup MR. Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities. Mol Cell Biol. 2002 Jun;22(11):3621-32. PMID:11997499
↑ Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S, Rastinejad F. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell. 2003 Apr;11(4):1093-100. PMID:12718893

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1osv"

@@ Line 3: / Line 3: @@
 <StructureSection load='1osv' size='340' side='right'caption='[[1osv]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1osv]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OSV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1osv]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OSV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CHC:6-ETHYL-CHENODEOXYCHOLIC+ACID'>CHC</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHC:6-ETHYL-CHENODEOXYCHOLIC+ACID'>CHC</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1osv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osv OCA], [http://pdbe.org/1osv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1osv RCSB], [http://www.ebi.ac.uk/pdbsum/1osv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1osv 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=1osv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1osv OCA], [https://pdbe.org/1osv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1osv RCSB], [https://www.ebi.ac.uk/pdbsum/1osv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1osv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/NR1H4_RAT NR1H4_RAT]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) and activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 within its gene locus (By similarity). [[http://www.uniprot.org/uniprot/NCOA2_MOUSE NCOA2_MOUSE]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:12507421</ref> <ref>PMID:11997499</ref>
+[[https://www.uniprot.org/uniprot/NR1H4_RAT NR1H4_RAT]] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) and activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 within its gene locus (By similarity). [[https://www.uniprot.org/uniprot/NCOA2_MOUSE NCOA2_MOUSE]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:12507421</ref> <ref>PMID:11997499</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1osv

From Proteopedia

Revision as of 09:21, 8 September 2021

STRUCTURAL BASIS FOR BILE ACID BINDING AND ACTIVATION OF THE NUCLEAR RECEPTOR FXR

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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