Estrogen-related receptor: Difference between revisions

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== Function ==
== Function ==


'''Estrogen-related receptor''' (ERR) binds to estrogen response elements on DNA and modulates transcription in response to [[Hormone|hormone]]. There are 3 classes of ERR : ERRα, ERRβ and ERRγ.
'''Estrogen-related receptor''' (ERR) binds to estrogen response elements on DNA and modulates transcription in response to [[Hormone|hormone]]. It is a [[Nuclear receptors|nuclear receptor]]. There are 3 classes of ERR : ERRα, ERRβ and ERRγ.
*'''ERR alpha''' regulates cellular metabolism and function<ref>PMID:32121253</ref>.
*'''ERR beta''' is expressed in the inner ear and controls the development of its endolymph-producing cells<ref>PMID:17765677</ref>.
*'''ERR gamma''' regulates the perinatal switch to oxidative metabolism in the myocardium<ref>PMID:20418374</ref>.
 
See also [[Intracellular receptors]]


== Relevance ==
== Relevance ==
Line 10: Line 15:
== Structural insights ==
== Structural insights ==


<scene name='50/501401/Cv/2'>Binding of nuclear receptor corepressor 2 peptide and 4-hydroxytamoxifen</scene> to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and tamoxifen are nestled between 4 alpha helices in the ERR active site <ref>PMID:16990259</ref>.   
<scene name='50/501401/Cv/4'>Binding of nuclear receptor corepressor 2 peptide and 4-hydroxytamoxifen</scene> to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and <scene name='50/501401/Cv/5'>tamoxifen</scene> are nestled between 4 alpha helices in the ERR active site <ref>PMID:16990259</ref>.   
</StructureSection>


==3D structures of estrogen-related receptor==
==3D structures of estrogen-related receptor==
[[Estrogen-related receptor 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*ERR
 
**[[1xb7]], [[3d24]] – hERR ligand-binding domain + peroxisome proliferator activated receptor coactivator 1 peptide – human<br />[[2pjl]] - hERR ligand-binding domain (mutant) + inverse agonist<br />
**[[3k6p]] - hERR ligand-binding domain + ligand
 
*ERRβ
 
**[[1lo1]] – hERR DNA-binding domain + DNA - NMR
 
*ERRγ


**[[2gp7]], [[2zbs]] - hERR ligand-binding domain<br />
**[[1kv6]], [[1tfc]] – hERR ligand-binding domain + steroid receptor coactivator 1 2nd NR-Box <br />
**[[2gpo]], [[2gpp]] - hERR ligand-binding domain + nuclear receptor-interacting protein 1 peptide<br />
**[[2ewp]] - hERR ligand-binding domain + tamoxifen analog<br />
**[[2gpu]], [[2p7z]] - hERR ligand-binding domain + 4-hydroxytamoxifen<br />
**[[2e2r]], [[2p7g]] - hERR ligand-binding domain + bisphenol A<br />
**[[2zkc]] - hERR ligand-binding domain + bisphenol Z<br />
**[[2zas]] - hERR ligand-binding domain + bisphenol A derivative<br />
**[[2p7a]] - hERR ligand-binding domain + methyl phenol<br />
**[[2gpv]] - hERR ligand-binding domain + nuclear receptor corepressor 2 peptide + 4-hydroxytamoxifen<br />
**[[1s9p]], [[1s9q]] - mERR ligand-binding domain + diethylstilbesterol – mouse<br />
**[[1vjb]] - mERR ligand-binding domain + 4-hydroxytamoxifen<br />
}}
== References ==
== References ==
<references/>
<references/>

Latest revision as of 12:29, 20 June 2024

Function

Estrogen-related receptor (ERR) binds to estrogen response elements on DNA and modulates transcription in response to hormone. It is a nuclear receptor. There are 3 classes of ERR : ERRα, ERRβ and ERRγ.

  • ERR alpha regulates cellular metabolism and function[1].
  • ERR beta is expressed in the inner ear and controls the development of its endolymph-producing cells[2].
  • ERR gamma regulates the perinatal switch to oxidative metabolism in the myocardium[3].

See also Intracellular receptors

Relevance

ERR plays a role in energy homeostasis and cancer[4]. ERRα and ERRγ are overexpressed in breast cancer and can serve as prognostic markers or therapeutic targets.

Structural insights

to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and are nestled between 4 alpha helices in the ERR active site [5].

3D structures of estrogen-related receptor

Estrogen-related receptor 3D structures


Human estrogen-related receptor γ ligand-binding domain (cyan, grey, green, yellow, pink, purple) complex with nuclear receptor corepressor 2 peptide (dark red, orange) and 4-hydroxytamoxifen (PDB code 2gpv)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Tripathi M, Yen PM, Singh BK. Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases. Int J Mol Sci. 2020 Feb 28;21(5):1645. PMID:32121253 doi:10.3390/ijms21051645
  2. ↑ Chen J, Nathans J. Estrogen-related receptor beta/NR3B2 controls epithelial cell fate and endolymph production by the stria vascularis. Dev Cell. 2007 Sep;13(3):325-37. PMID:17765677 doi:10.1016/j.devcel.2007.07.011
  3. ↑ Rangwala SM, Wang X, Calvo JA, Lindsley L, Zhang Y, Deyneko G, Beaulieu V, Gao J, Turner G, Markovits J. Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity. J Biol Chem. 2010 Jul 16;285(29):22619-29. PMID:20418374 doi:10.1074/jbc.M110.125401
  4. ↑ Ariazi EA, Jordan VC. Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. PMID:16515477
  5. ↑ Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT. X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation. J Biol Chem. 2006 Dec 8;281(49):37773-81. Epub 2006 Sep 21. PMID:16990259 doi:http://dx.doi.org/10.1074/jbc.M608410200

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Michal Harel, Wayne Decatur, Alexander Berchansky
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