Glucocorticoid receptor: Difference between revisions

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*<StructureSection load='3g6r' size='350' side='right' caption='Rat glucocorticoid receptor DNA-binding domain dimer complex with DNA and Zn+2 ions (grey) (PDB entry [[3g6r]])' scene=''>
<StructureSection load='3g6r' size='350' side='right' caption='Rat glucocorticoid receptor DNA-binding domain dimer complex with DNA and Zn+2 ions (grey) (PDB entry [[3g6r]])' scene=''>
== Function ==
== Function ==


'''Glucocorticoid receptor''' (GCR) is the nuclear receptor binding cortisol and glucocorticoids.  GCR regulates genes involved in development, metabolism and immune response.  GCR interacts with nuclear receptor coactivator 2 (NCOA2) which promotes DNA transcription by acylating histones<ref>PMID:17132855</ref>.
'''Glucocorticoid receptor''' (GCR) is the [[Nuclear receptors|nuclear receptor]] binding cortisol and [[glucocorticoids]].  GCR regulates genes involved in development, metabolism and immune response.  GCR interacts with nuclear receptor coactivator 2 (NCOA2) which promotes DNA transcription by acylating histones<ref>PMID:17132855</ref>.
 
See also:
*[[Glucocorticoids]] 
*[[Intracellular receptors]]
*[[Steroid Hormones and their receptors]].


== Relevance ==
== Relevance ==
Line 8: Line 13:
The glucocorticoid-bound GCR can either up-regulate the expression of anti-inflammatory proteins (transactivation) or repress the expression of pro-inflammatory proteins (transrepression)<ref>PMID:24113652</ref>.
The glucocorticoid-bound GCR can either up-regulate the expression of anti-inflammatory proteins (transactivation) or repress the expression of pro-inflammatory proteins (transrepression)<ref>PMID:24113652</ref>.


== Structural highlights ==
== Disease ==


GCR contains 5 domains: N terminal regulatory domain; DNA-binding domain (DBD) residues 417-506; hinge region; ligand-binding domain (LBD) residues 521-777 and C terminal domain.
[[Budesonide]] is an agonist of GCR and is used as medication for asthma and inflammatory bowel diseases like chronic obstructive pulmonary disease<ref>PMID:15641626</ref>.
</StructureSection>
==3D structures of glucocorticoid receptor==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
== Structural highlights ==
{{#tree:id=OrganizedByTopic|openlevels=0|


*Glucocorticoid receptor residues 89-158
GCR contains 5 domains: N terminal regulatory domain; DNA-binding domain (DBD) residues 417-506; hinge region; ligand-binding domain (LBD) residues 521-777 and C terminal domain. <scene name='89/895670/Cv/4'>Human glucocorticoid receptor ligand-binding domain bound to dexamethasone</scene> ([[1m2z]]).


**[[5va7]], [[5va0]] - hGCR + DNA – human<br />
<scene name='96/962959/Tert/1'>Glucocorticoid Receptor in complex with budesonide</scene> ([[5nfp]]).


*Glucocorticoid receptor DBD domain residues 391-480
<scene name='96/962959/Binding_site/1'>Budesonide binding site</scene>. Water molecule is shown as red sphere.


**[[1gdc]], [[2gda]], [[1rgd]] – rGCR DBD – NMR – rat<br />
<scene name='97/973067/Overall/1'>Crystal Structure of mometasone furoate-bound glucocorticoid receptor ligand binding domain</scene> ([[4p6w]]).
**[[3g9p]], [[3fyl]], [[3g6p]], [[3g6q]], [[3g6r]], [[3g6t]], [[3g6u]], [[3g8u]], [[3g8x]], [[3g97]], [[3g99]], [[3g9i]], [[3g9m]], [[3g9j]], [[3g9o]], [[1glu]], [[1lat]], [[1r4o]], [[1r4r]] - rGCR DBD + DNA<br />
**[[4hn5]], [[4hn6]], [[5emp]], [[5emq]], [[5emc]], [[5e69]], [[5e6a]], [[5e6b]], [[5e6c]], [[5e6d]], [[5cbx]], [[5cby]], [[5cbz]] - hGCR DBD + DNA – human<br />
**[[5cc1]] - hGCR DBD (mutant) + DNA <br />


*Glucocorticoid receptor LBD domain residues 500-777 complex with NCOA peptide
<scene name='97/973067/Binding_site/1'>Mometasone furoate binding site</scene>.


**[[4mdd]] - hGCR LBD (mutant) + NCOA1 peptide + non-steroidal agonist<br />
==3D structures of glucocorticoid receptor==
**[[3h52]] - hGCR LBD (mutant) + NCOA1 peptide + steroid<br />
[[Glucocorticoid receptor 3D structures]]
**[[4udc]], [[4udd]] - hGCR LBD (mutant) + NCOA2 peptide <br />
**[[1m2z]], [[3cld]], [[3bqd]], [[4lsj]], [[4p6w]], [[4p6x]], [[1p93]] - hGCR LBD (mutant) + NCOA2 peptide + steroid <br />
**[[3e7c]], [[4csj]], [[5g3j]], [[5g5w]], [[5g3j]] - hGCR LBD (mutant) + NCOA2 peptide + non-steroidal agonist<br />
**[[3k23]] - hGCR LBD (mutant) + NCOA2 peptide + prolinamide<br />
**[[6el9]], [[6el6]], [[6el7]], [[5nft]] - hGCR LBD + NCOA2 peptide + modulator<br />
**[[5nfp]] - hGCR LBD + NCOA2 peptide + drug<br />
**[[3gn8]] - hGCR LBD + NCOA2 peptide + steroid<br />
**[[4e2j]] - GCR LBD ancestral + NCOA2 peptide + steroid<br />
**[[3mne]], [[3mno]], [[3mnp]] - GCR LBD (mutant) + NCOA2 peptide + steroid – mouse<br />


*Glucocorticoid receptor LBD domain other complexes
</StructureSection>
 
**[[3ry9]] - anGCR LBD ancestral + steroid<br />
**[[1nhz]] – hGCR LBD (mutant) + steroid<br />
**[[5uc3]] - hGCR LBD (mutant) + RU-486<br />
**[[3k22]] - hGCR LBD (mutant) + transcriptional intermediary factor 2  peptide + alaninamide<br />
 
 
*Glucocorticoid receptor 2
 
**[[5ufs]] – anGCR2 LBD + SHP coregulatory + triamcinolone acetonide <br />
**[[4e2j]] – anGCR2 LBD ancestral + NCOA2 peptide + steroid<br />
**[[5uc1]] – GCR2 LBD + RU-486 – ''Heterocephalus glaber''<br />


}}
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 13:09, 16 January 2024

Function

Glucocorticoid receptor (GCR) is the nuclear receptor binding cortisol and glucocorticoids. GCR regulates genes involved in development, metabolism and immune response. GCR interacts with nuclear receptor coactivator 2 (NCOA2) which promotes DNA transcription by acylating histones[1].

See also:

Relevance

The glucocorticoid-bound GCR can either up-regulate the expression of anti-inflammatory proteins (transactivation) or repress the expression of pro-inflammatory proteins (transrepression)[2].

Disease

Budesonide is an agonist of GCR and is used as medication for asthma and inflammatory bowel diseases like chronic obstructive pulmonary disease[3].

Structural highlights

GCR contains 5 domains: N terminal regulatory domain; DNA-binding domain (DBD) residues 417-506; hinge region; ligand-binding domain (LBD) residues 521-777 and C terminal domain. (1m2z).

(5nfp).

. Water molecule is shown as red sphere.

(4p6w).

.

3D structures of glucocorticoid receptor

Glucocorticoid receptor 3D structures


Rat glucocorticoid receptor DNA-binding domain dimer complex with DNA and Zn+2 ions (grey) (PDB entry 3g6r)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev. 2006 Dec;58(4):782-97. PMID:17132855 doi:http://dx.doi.org/10.1124/pr.58.4.9
  2. ↑ Finsterwald C, Alberini CM. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies. Neurobiol Learn Mem. 2014 Jul;112:17-29. doi: 10.1016/j.nlm.2013.09.017. Epub, 2013 Oct 7. PMID:24113652 doi:http://dx.doi.org/10.1016/j.nlm.2013.09.017
  3. ↑ Selroos O, Edsbäcker S, Hultquist C. Once-daily inhaled budesonide for the treatment of asthma: clinical evidence and pharmacokinetic explanation. J Asthma. 2004;41(8):771-90. PMID:15641626 doi:10.1081/jas-200038344

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Michal Harel, Alexander Berchansky
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