Liver X receptor

From Proteopedia

Contents 1 Function 2 Disease 3 Relevance 4 Structural highlights Function Liver X receptors (LXR) are ligand-activated transcription factors of the nuclear receptor family. There are two LXR isoforms α and β which form heterodimers with retinoic X receptor upon activation and bind to the LXR response element found in the promoter region of the target genes[1]. LXR is a lipogenic transcription factor[2]. LXRs modulate the expression of genes in cholesterol and lipid metabolism in response to changes in cellular cholesterol status. Liver X receptor alpha has a role in regulating innate immunity at the genomic level. Liver X receptor beta is an important transcription factor promoting the survival of single-positive thymocytes[3]. See also Intracellular receptors Disease Treatment of mice demonstrating Wilson disease with LXR agonist reduced disease manifestations without worsening neurological symptoms associated with the conventional therapy based on copper chelation[4]. Relevance LXRs have emerged as promising drug targets for anti-atherosclerotic therapies[5]. Structural highlights Human liver X receptor β ligand binding domain complex with retinoic X receptor β and modulator. LXR modulator binds to the LXR in the LXR/retinoic X receptor β heterodimer in a hydrophobic pocket[6].

spinqualitylabelsall models Human liver X receptor β ligand binding domain (deepskyblue) complex with retinoic X receptor β (green) and modulator (PDB code 5kya) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of liver X receptor

Updated on 10-July-2024

Liver X receptor α

5avl, 5avl, 5hjs, 3ipq, 3ips, 3ipu – hLXR LBD + NCOA-1 peptide + agonist - human

1uhl – hLXR LBD + retinoic X receptor β + NCOA-2

2acl – mLXR + retinoic X receptor α + agonist – mouse

Liver X receptor β

1upv, 1upw, 5jy3, 3kfc, 4rak, 6s4n, 6s4t, 6s4u, 6s5k – hLXR LBD + agonist

6k9g, 6k9h, 6k9m – hLXR LBD (mutant) + agonist

1pq6, 1pqc, 1pq9 – hLXR LBD + ligand

6jio – hLXR LBD (mutant) + ligand

5i4v – hLXR LBD + retinoic X receptor β + agonist

5kyj, 5kya – hLXR LBD + retinoic X receptor β + modulator

3fal – hLXR LBD + retinoic X receptor β + modulator + retinoic acid

5hjp – hLXR LBD + retinoic X receptor β + agonist

4nqa – hLXR LBD + retinoic X receptor β + NCOA-2 peptide + DNA

4dk7, 4dk8, 5avi – hLXR LBD + NCOA-1 peptide + agonist

1p8d – hLXR LBD + NCOA-1 peptide + cholesterol derivative

3l0e – hLXR LBD + NCOA-2 peptide + inhibitor

References

1. ↑ Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol. 2008 Dec;59 Suppl 7:31-55. PMID:19258656
2. ↑ Cha JY, Repa JJ. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem. 2007 Jan 5;282(1):743-51. doi: 10.1074/jbc.M605023200. Epub 2006 Nov, 14. PMID:17107947 doi:http://dx.doi.org/10.1074/jbc.M605023200
3. ↑ Huang H, Wu X, Meng D, Feng Y, Zhou L, Liu Z, Tang S, Li X, Cao Y, He H, Xie Z, Zhang J, Chen Y, Zhao T, Wu Y, Zhou X. Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression. Cell Mol Immunol. 2021 Aug;18(8):1969-1980. PMID:32963358 doi:10.1038/s41423-020-00546-y
4. ↑ Hamilton JP, Koganti L, Muchenditsi A, Pendyala VS, Huso D, Hankin J, Murphy RC, Huster D, Merle U, Mangels C, Yang N, Potter JJ, Mezey E, Lutsenko S. Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice. Hepatology. 2016 Jun;63(6):1828-41. doi: 10.1002/hep.28406. Epub 2016 Feb 22. PMID:26679751 doi:http://dx.doi.org/10.1002/hep.28406
5. ↑ Oosterveer MH, Grefhorst A, Groen AK, Kuipers F. The liver X receptor: control of cellular lipid homeostasis and beyond Implications for drug design. Prog Lipid Res. 2010 Oct;49(4):343-52. doi: 10.1016/j.plipres.2010.03.002. Epub, 2010 Apr 2. PMID:20363253 doi:http://dx.doi.org/10.1016/j.plipres.2010.03.002
6. ↑ Tice CM, Noto PB, Fan KY, Zhao W, Lotesta SD, Dong C, Marcus AP, Zheng YJ, Chen G, Wu Z, Van Orden R, Zhou J, Bukhtiyarov Y, Zhao Y, Lipinski K, Howard L, Guo J, Kandpal G, Meng S, Hardy A, Krosky P, Gregg RE, Leftheris K, McKeever BM, Singh SB, Lala D, McGeehan GM, Zhuang L, Claremon DA. Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core. Bioorg Med Chem Lett. 2016 Aug 29. pii: S0960-894X(16)30921-0. doi:, 10.1016/j.bmcl.2016.08.089. PMID:27599745 doi:http://dx.doi.org/10.1016/j.bmcl.2016.08.089