1xvp: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: left|200px<br /> <applet load="1xvp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xvp, resolution 2.6Å" /> '''crystal structure of...
 
No edit summary
 
(16 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1xvp.gif|left|200px]]<br />
<applet load="1xvp" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1xvp, resolution 2.6&Aring;" />
'''crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO'''<br />


==Overview==
==crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO==
The X-ray crystal structure of the human constitutive androstane receptor, (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds, light on the mechanism of ligand-independent activation of transcription, by nuclear receptors. CAR contains a single-turn Helix X that restricts, the conformational freedom of the C-terminal AF2 helix, favoring the, active state of the receptor. Helix X and AF2 sit atop four amino acids, that shield the CAR ligand binding pocket. A fatty acid ligand was, identified in the RXRalpha binding pocket. The endogenous RXRalpha ligand, combined with stabilizing interactions from the heterodimer interface, served to hold RXRalpha in an active conformation. The structure suggests, that upon translocation, CAR/RXRalpha heterodimers are preorganized in an, active conformation in cells such that they can regulate transcription of, target genes. Insights into the molecular basis of CAR constitutive, activity can be exploited in the design of inverse agonists as drugs for, treatment of obesity.
<StructureSection load='1xvp' size='340' side='right'caption='[[1xvp]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xvp]] is a 8 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=1XVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XVP 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CID:6-(4-CHLOROPHENYL)IMIDAZO[2,1-B][1,3]THIAZOLE-5-CARBALDEHYDE+O-(3,4-DICHLOROBENZYL)OXIME'>CID</scene>, <scene name='pdbligand=F15:PENTADECANOIC+ACID'>F15</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=1xvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xvp OCA], [https://pdbe.org/1xvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xvp RCSB], [https://www.ebi.ac.uk/pdbsum/1xvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xvp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RXRA_HUMAN 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.<ref>PMID:10195690</ref> <ref>PMID:11162439</ref> <ref>PMID:11915042</ref> <ref>PMID:20215566</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xv/1xvp_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xvp ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Adrenocortical tumor, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Carney complex, type 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Myxoma, intracardiac OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Pigmented adrenocortical disease, primary, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]], Spastic paraplegia-7 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602783 602783]], Thyroid carcinoma, papillary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=188830 188830]]
*[[Retinoid X receptor 3D structures|Retinoid X receptor 3D structures]]
 
== References ==
==About this Structure==
<references/>
1XVP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with F15 and CID as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XVP OCA].
__TOC__
 
</StructureSection>
==Reference==
A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer., Xu RX, Lambert MH, Wisely BB, Warren EN, Weinert EE, Waitt GM, Williams JD, Collins JL, Moore LB, Willson TM, Moore JT, Mol Cell. 2004 Dec 22;16(6):919-28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15610735 15610735]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Lambert, M.H.]]
[[Category: Lambert MH]]
[[Category: Moore, J.T.]]
[[Category: Moore JT]]
[[Category: Moore, L.B.]]
[[Category: Moore LB]]
[[Category: Waitt, G.M.]]
[[Category: Waitt GM]]
[[Category: Warren, E.N.]]
[[Category: Warren EN]]
[[Category: Weinert, E.E.]]
[[Category: Weinert EE]]
[[Category: Williams, J.D.]]
[[Category: Williams JD]]
[[Category: Willson, T.M.]]
[[Category: Willson TM]]
[[Category: Wisely, B.B.]]
[[Category: Wisely BB]]
[[Category: Xu, R.X.]]
[[Category: Xu RX]]
[[Category: CID]]
[[Category: F15]]
[[Category: car]]
[[Category: citco]]
[[Category: rxr]]
[[Category: src1]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:11:27 2007''

Latest revision as of 11:53, 14 February 2024

crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCOcrystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid and CITCO

Structural highlights

1xvp is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
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]

Evolutionary Conservation

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

1xvp, resolution 2.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1xvp&oldid=4056466"