Retinoid X receptor

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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.

There are 3 classes of RXR: α, β and γ.

  • RXRα plays a pivotal role in liver metabolism[2].
  • RXRγ mediates the anti proliferative effects of retinoid acid.

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. The ligand-binding residues are conserved in the 3 types of RXR

[5].

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

Drag the structure with the mouse to rotate

3D structures of retinoid X receptor3D structures of retinoid X receptor

Updated on 08-August-2016

ReferencesReferences

  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:http://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:http://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:http://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:http://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

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

Michal Harel, Alexander Berchansky, Joel L. Sussman
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