1xls

From Proteopedia

(Difference between revisions)

Revision as of 10:06, 6 January 2021

Crystal structure of the mouse CAR/RXR LBD heterodimer bound to TCPOBOP and 9cRA and a TIF2 peptide containg the third LXXLL motifs

Structural highlights

1xls is a 16 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	human (HUMAN), mouse (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RXRA_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.^[1] ^[2] ^[3] ^[4] [NCOA2_RAT] 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. [NR1I3_MOUSE] Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element (By similarity).^[5]

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

Constitutive androstane receptor (CAR) induces xenobiotic, bilirubin, and thyroid hormone metabolism as a heterodimer with the retinoid X receptor (RXR). Unlike ligand-dependent nuclear receptors, CAR is constitutively active. Here, we report the heterodimeric structure of the CAR and RXR ligand binding domains (LBDs), which reveals an unusually large dimerization interface and a small CAR ligand binding pocket. Constitutive CAR activity appears to be mediated by the compact nature of the CAR LBD that displays several unique features including a shortened AF2 helix and helix H10, which are linked by a two-turn helix that normally adopts an extended loop in other receptors, and an extended helix H2 that stabilizes the canonical LBD fold by packing tightly against helix H3. These structural observations provide a molecular framework for understanding the atypical transcriptional activation properties of CAR.

The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.,Suino K, Peng L, Reynolds R, Li Y, Cha JY, Repa JJ, Kliewer SA, Xu HE Mol Cell. 2004 Dec 22;16(6):893-905. PMID:15610733^[6]

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

References

↑ Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690
↑ Harish S, Ashok MS, Khanam T, Rangarajan PN. Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function. Biochem Biophys Res Commun. 2000 Dec 29;279(3):853-7. PMID:11162439 doi:10.1006/bbrc.2000.4043
↑ Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. PMID:11915042 doi:10.1053/jhep.2002.32470
↑ Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338
↑ Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys. 1999 Sep 1;369(1):11-23. PMID:10462436 doi:http://dx.doi.org/10.1006/abbi.1999.1351
↑ Suino K, Peng L, Reynolds R, Li Y, Cha JY, Repa JJ, Kliewer SA, Xu HE. The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization. Mol Cell. 2004 Dec 22;16(6):893-905. PMID:15610733 doi:10.1016/j.molcel.2004.11.036

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/1xls"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the mouse CAR/RXR LBD heterodimer bound to TCPOBOP and 9cRA and a TIF2 peptide containg the third LXXLL motifs==
-<StructureSection load='1xls' size='340' side='right' caption='[[1xls]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
+<StructureSection load='1xls' size='340' side='right'caption='[[1xls]], [[Resolution|resolution]] 2.96&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1xls]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XLS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1xls]] is a 16 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XLS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XLS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene>, <scene name='pdbligand=TCD:3,5-DICHLORO-2-{4-[(3,5-DICHLOROPYRIDIN-2-YL)OXY]PHENOXY}PYRIDINE'>TCD</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9CR:(9CIS)-RETINOIC+ACID'>9CR</scene>, <scene name='pdbligand=TCD:3,5-DICHLORO-2-{4-[(3,5-DICHLOROPYRIDIN-2-YL)OXY]PHENOXY}PYRIDINE'>TCD</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">human ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), mouse ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1xls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xls OCA], [http://pdbe.org/1xls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xls RCSB], [http://www.ebi.ac.uk/pdbsum/1xls PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xls ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1xls FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xls OCA], [http://pdbe.org/1xls PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xls RCSB], [http://www.ebi.ac.uk/pdbsum/1xls PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xls ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xl/1xls_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xl/1xls_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 29: @@
 </div>
 <div class="pdbe-citations 1xls" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
 == References ==
 <references/>
@@ Line 34: / Line 37: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Cha, J Y]]

1xls

From Proteopedia

Revision as of 10:06, 6 January 2021

Crystal structure of the mouse CAR/RXR LBD heterodimer bound to TCPOBOP and 9cRA and a TIF2 peptide containg the third LXXLL motifs

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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