Retinoid X receptor: Difference between revisions

Latest revision as of 09:38, 12 January 2023

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Structure of human retinoid X receptorα ligand-binding domain complex with 9-cis retinoic acid (PDB entry 1fby)

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Function

Retinoid X receptor (RXR) is a nuclear receptor activated by 9-cis retinoic acid. RXR makes a heterodimer with subfamily 1 nuclear receptors including retinoic acid receptor (RAR). In the absence of ligand, the RAR/RXR complex binds the hormone response elements complexed with corepressor protein. Upon binding of the ligand, the corepressor disassociates from the receptor and associates with the coactivator leading to transcription activation. RXR contains a DNA-binding domain (DBD) and ligand-binding domain (LBD)^[1]. For additional details on RXR-α see RA Mediated T-reg Differentiation.

Relevance

RXRγ is involved in working memory and despair behavior^[3]. RXR pathway is a positive regulator of myelin debris clearance and has a role in age-related decline in remyelination^[4].

Structural highlights

9-cis retinoid acid binds to RXRα LBD in a hydrophobic pocket. Hydrophobic, Polar. Water molecules are shown as red spheres. 9-cis retinoid acid is in a hydrophobic pocket. The ligand-binding residues are conserved in the 3 classes of RXR ^[5].

3D structures of retinoid X receptor

Retinoid X receptor 3D structures

↑ Dawson MI, Xia Z. The retinoid X receptors and their ligands. Biochim Biophys Acta. 2012 Jan;1821(1):21-56. doi: 10.1016/j.bbalip.2011.09.014. , Epub 2011 Oct 1. PMID:22020178 doi:https://dx.doi.org/10.1016/j.bbalip.2011.09.014
↑ Wu Y, Zhang X, Bardag-Gorce F, Robel RC, Aguilo J, Chen L, Zeng Y, Hwang K, French SW, Lu SC, Wan YJ. Retinoid X receptor alpha regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver. Mol Pharmacol. 2004 Mar;65(3):550-7. PMID:14978233 doi:https://dx.doi.org/10.1124/mol.65.3.550
↑ Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, Endo Y, Perez E, de Lera AR, Chambon P, Krezel W. Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry. 2011 Apr 15;69(8):788-94. doi: 10.1016/j.biopsych.2010.12.017., Epub 2011 Feb 21. PMID:21334601 doi:https://dx.doi.org/10.1016/j.biopsych.2010.12.017
↑ Natrajan MS, de la Fuente AG, Crawford AH, Linehan E, Nunez V, Johnson KR, Wu T, Fitzgerald DC, Ricote M, Bielekova B, Franklin RJ. Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination. Brain. 2015 Dec;138(Pt 12):3581-97. doi: 10.1093/brain/awv289. Epub 2015 Oct 12. PMID:26463675 doi:https://dx.doi.org/10.1093/brain/awv289
↑ Egea PF, Mitschler A, Rochel N, Ruff M, Chambon P, Moras D. Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid. EMBO J. 2000 Jun 1;19(11):2592-601. PMID:10835357 doi:10.1093/emboj/19.11.2592

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Dawson MI, Xia Z. The retinoid X receptors and their ligands. Biochim Biophys Acta. 2012 Jan;1821(1):21-56. doi: 10.1016/j.bbalip.2011.09.014. , Epub 2011 Oct 1. PMID:22020178 doi:https://dx.doi.org/10.1016/j.bbalip.2011.09.014

[2] Wu Y, Zhang X, Bardag-Gorce F, Robel RC, Aguilo J, Chen L, Zeng Y, Hwang K, French SW, Lu SC, Wan YJ. Retinoid X receptor alpha regulates glutathione homeostasis and xenobiotic detoxification processes in mouse liver. Mol Pharmacol. 2004 Mar;65(3):550-7. PMID:14978233 doi:https://dx.doi.org/10.1124/mol.65.3.550

[3] Wietrzych-Schindler M, Szyszka-Niagolov M, Ohta K, Endo Y, Perez E, de Lera AR, Chambon P, Krezel W. Retinoid x receptor gamma is implicated in docosahexaenoic acid modulation of despair behaviors and working memory in mice. Biol Psychiatry. 2011 Apr 15;69(8):788-94. doi: 10.1016/j.biopsych.2010.12.017., Epub 2011 Feb 21. PMID:21334601 doi:https://dx.doi.org/10.1016/j.biopsych.2010.12.017

[4] Natrajan MS, de la Fuente AG, Crawford AH, Linehan E, Nunez V, Johnson KR, Wu T, Fitzgerald DC, Ricote M, Bielekova B, Franklin RJ. Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination. Brain. 2015 Dec;138(Pt 12):3581-97. doi: 10.1093/brain/awv289. Epub 2015 Oct 12. PMID:26463675 doi:https://dx.doi.org/10.1093/brain/awv289

[5] Egea PF, Mitschler A, Rochel N, Ruff M, Chambon P, Moras D. Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid. EMBO J. 2000 Jun 1;19(11):2592-601. PMID:10835357 doi:10.1093/emboj/19.11.2592

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@@ Line 1: / Line 1: @@
-<StructureSection load='1g5y' size='400' side='right' caption='Structure of human retinoid X receptor ligand-binding domain tetramer complex with retinoid  (PDB entry [[1g5y]])' scene=''>
+<StructureSection load='' size='350' side='right' caption='Structure of human retinoid X receptor α ligand-binding domain complex with 9-cis retinoic acid (PDB entry [[1fby]])' scene='51/516465/Cv/1'>
+__TOC__
-'''Retinoid X receptor''' (RXR) is a nuclear receptor activated by 9-cis retinoic acid.  RXR makes a heterodimer with subfamily 1 nuclear receptors including retinoic acid receptor (RAR).  In the absence of ligand, the RAR/RXR complex binds the hormone response elements complexed with corepressor protein.  Upon binding of the ligand, the corepressor disassociates from the receptor and associates with the coactivator leading to transcription activation.  RAR contains a DNA-binding domain (DBD) and ligand-binding domain (LBD).  There are 3 classes of RXR: α, β and γ.
+== Function ==
+'''Retinoid X receptor''' (RXR) is a [[Nuclear receptors|nuclear receptor]] activated by 9-''cis'' retinoic acid.  RXR makes a heterodimer with subfamily 1 nuclear receptors including [[Retinoic acid receptor|retinoic acid receptor]] (RAR). In the absence of ligand, the RAR/RXR complex binds the hormone response elements complexed with corepressor protein.  Upon binding of the ligand, the corepressor disassociates from the receptor and associates with the coactivator leading to transcription activation.  RXR contains a DNA-binding domain (DBD) and ligand-binding domain (LBD)<ref>PMID:22020178</ref>.  For additional details on RXR-α see [[RA Mediated T-reg Differentiation]].
-==3D structures of retinoid X receptor==
+See also [[Intracellular receptors]]
-===Retinoid X receptor α===
+There are 3 classes of RXR: α, β and γ.  <br />
+*'''RXRα''' plays a pivotal role in liver metabolism<ref>PMID:14978233</ref>.<br />
+*'''RXRγ''' mediates the anti proliferative effects of retinoid acid.<br />
-[[3nsp]], [[1lbd]], [[1g1u]] - hRXR LBD – human<br />
+== Relevance ==
-[[1rxr]] – hRXR DBD (mutant) – NMR<br />
+RXRγ is involved in working memory and despair behavior<ref>PMID:21334601</ref>.  RXR pathway is a positive regulator of myelin debris clearance and has a role in age-related decline in remyelination<ref>PMID:26463675</ref>. <br />
-[[1by4]] – hRXR + DNA<br />
-[[1g5y]] - hRXR LBD + retinoid<br />
-[[1dkf]] – mRXR LBD + mRAR LBD – mouse<br />
-[[1dsz]] - hRXR LBD + hRAR LBD + DNA<br />
-[[1fby]] - hRXR LBD + 9-cis retinoic acid<br />
-[[3nsq]] - hRXR LBD + antagonist<br />
-[[3a9e]] - hRXR LBD + hRAR LBD + coactivator peptide<br />
-[[3fug]] - hRXR LBD + coactivator peptide<br />
-[[3fc6]] – hRXR LBD + NR1H3 protein<br />
-[[3r29]] - hRXR LBD + corepressor peptide SMRT2<br />
-[[3r2a]] - hRXR LBD + corepressor peptide SMRT2 + antagonist<br />
-[[3h0a]], [[1fm6]], [[1fm9]], [[1k74]] - hRXR LBD + PPAR-γ + 9-cis retinoic acid + coactivator peptide<br />
-[[1rdt]] - hRXR LBD + PPAR-γ + coactivator peptide<br />
-[[3dzu]], [[3dzy]], [[3e00]] - hRXR LBD + PPAR-γ + 9-cis retinoic acid + coactivator peptide + DNA<br />
-[[3oap]] - hRXR LBD + 9-cis retinoic acid + coactivator peptide<br />
-[[3uvv]] - hRXR LBD + 9-cis retinoic acid + thyronine + thyroid hormone receptor α<br />
-[[3ozj]] - hRXR LBD + bigelovin + coactivator peptide<br />
-[[3pcu]] - hRXR LBD + rutamarin + coactivator peptide<br />
-[[2zxz]], [[2zy0]], [[3r5m]], [[1mzn]], [[1mv9]], [[1mvc]] - hRXR LBD + agonist + coactivator peptide<br />
-[[2acl]] - hRXR LBD + agonist + oxysterols receptor α<br />
-[[3fal]] - hRXR LBD + modulator + oxysterols receptor α + 9-cis retinoic acid<br />
-[[3kwy]] - hRXR LBD + triphenyltin + coactivator peptide<br />
-[[3e94]] - hRXR LBD + tributylin + coactivator peptide<br />
-[[2p1t]], [[2p1u]], [[2p1v]] - hRXR LBD + retinoid + coactivator peptide<br />
-[[1xls]] - hRXR LBD (mutant) + orphan nuclear receptor NR1I3 + coactivator peptide<br />
-[[1xv9]] - hRXR LBD + orphan nuclear receptor NR1I3 + pregnane + coactivator peptide<br />
-[[1xvp]] - hRXR LBD + orphan nuclear receptor NR1I3 + CITCO + coactivator peptide<br />
-===Retinoid X receptor β===
+== Structural highlights ==
+<scene name='51/516465/Cv/4'>9-cis retinoid acid binds to RXRα LBD in a hydrophobic pocket</scene>. {{Template:ColorKey_Hydrophobic}},  {{Template:ColorKey_Polar}}. Water molecules are shown as red spheres. <scene name='51/516465/Cv/5'>9-cis retinoid acid is in a hydrophobic pocket</scene>. The ligand-binding residues are conserved in the 3 classes of RXR
-[[1xdk]] - mRXR LBD + mRAR LBD + thyroid receptor associated protein<br />
+<ref>PMID:10835357</ref>.
-[[1uhl]] - hRXR LBD + oxysterols receptor α + coactivator peptide<br />
+==3D structures of retinoid X receptor==
-[[1h9u]] – hRXR LBD + agonist
+[[Retinoid X receptor 3D structures]]
-===Retinoid X receptor γ===
+</StructureSection>
-[[2gl8]] – hRXR LBD
+== References ==
+<references/>
 [[Category:Topic Page]]

Retinoid X receptor: Difference between revisions

Latest revision as of 09:38, 12 January 2023

Contents

Function

Relevance

Structural highlights

3D structures of retinoid X receptor

References

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