4s15: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4s15]] is a 4 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=4S15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S15 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4s15]] is a 4 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=4S15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S15 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D8:(3BETA,4ALPHA,5BETA,14BETA)-3-HYDROXY-4-METHYLCHOLESTA-8,24-DIENE-4-CARBOXYLIC+ACID'>4D8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.897&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D8:(3BETA,4ALPHA,5BETA,14BETA)-3-HYDROXY-4-METHYLCHOLESTA-8,24-DIENE-4-CARBOXYLIC+ACID'>4D8</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4s15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s15 OCA], [https://pdbe.org/4s15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s15 RCSB], [https://www.ebi.ac.uk/pdbsum/4s15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s15 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=4s15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s15 OCA], [https://pdbe.org/4s15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s15 RCSB], [https://www.ebi.ac.uk/pdbsum/4s15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s15 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/RORA_HUMAN RORA_HUMAN] Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives.<ref>PMID:9862959</ref> <ref>PMID:11554739</ref> <ref>PMID:11053433</ref> <ref>PMID:14570920</ref> <ref>PMID:15790933</ref> <ref>PMID:15781255</ref> <ref>PMID:17512500</ref> <ref>PMID:18658046</ref> <ref>PMID:18005000</ref> <ref>PMID:12467577</ref>  
[https://www.uniprot.org/uniprot/RORA_HUMAN RORA_HUMAN] Orphan nuclear receptor. Binds DNA as a monomer to hormone response elements (HRE) containing a single core motif half-site preceded by a short A-T-rich sequence. This isomer binds to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'. Regulates a number of genes involved in lipid metabolism such as apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in cerebellum and photoreceptor development including PCP2, OPN1SW, OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal muscle development with MYOD1. Possible receptor for cholesterol or one of its derivatives.<ref>PMID:9862959</ref> <ref>PMID:11554739</ref> <ref>PMID:11053433</ref> <ref>PMID:14570920</ref> <ref>PMID:15790933</ref> <ref>PMID:15781255</ref> <ref>PMID:17512500</ref> <ref>PMID:18658046</ref> <ref>PMID:18005000</ref> <ref>PMID:12467577</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mice deficient in the nuclear hormone receptor RORgammat have defective development of thymocytes, lymphoid organs, Th17 cells, and type 3 innate lymphoid cells. RORgammat binds to oxysterols derived from cholesterol catabolism, but it is not clear whether these are its natural ligands. Here, we show that sterol lipids are necessary and sufficient to drive RORgammat-dependent transcription. We combined overexpression, RNAi, and genetic deletion of metabolic enzymes to study RORgamma-dependent transcription. Our results are consistent with the RORgammat ligand(s) being a cholesterol biosynthetic intermediate (CBI) downstream of lanosterol and upstream of zymosterol. Analysis of lipids bound to RORgamma identified molecules with molecular weights consistent with CBIs. Furthermore, CBIs stabilized the RORgamma ligand-binding domain and induced coactivator recruitment. Genetic deletion of metabolic enzymes upstream of the RORgammat-ligand(s) affected the development of lymph nodes and Th17 cells. Our data suggest that CBIs play a role in lymphocyte development potentially through regulation of RORgammat.
Identification of Natural RORgamma Ligands that Regulate the Development of Lymphoid Cells.,Santori FR, Huang P, van de Pavert SA, Douglass EF Jr, Leaver DJ, Haubrich BA, Keber R, Lorbek G, Konijn T, Rosales BN, Rozman D, Horvat S, Rahier A, Mebius RE, Rastinejad F, Nes WD, Littman DR Cell Metab. 2015 Feb 3;21(2):286-97. doi: 10.1016/j.cmet.2015.01.004. PMID:25651181<ref>PMID:25651181</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4s15" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 12:57, 1 March 2024

Crystal structure of the orphan nuclear receptor RORalpha ligand-binding domain in complex with 4alpha-caboxyl, 4beta-methyl-zymosterol (4ACD8)

4s15, resolution 1.90Å

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