1m2z: Difference between revisions

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{{Seed}}
[[Image:1m2z.png|left|200px]]


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==Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif==
The line below this paragraph, containing "STRUCTURE_1m2z", creates the "Structure Box" on the page.
<StructureSection load='1m2z' size='340' side='right'caption='[[1m2z]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1m2z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M2Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M2Z FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DEX:DEXAMETHASONE'>DEX</scene></td></tr>
{{STRUCTURE_1m2z| PDB=1m2z |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1m2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m2z OCA], [https://pdbe.org/1m2z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m2z RCSB], [https://www.ebi.ac.uk/pdbsum/1m2z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m2z ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[https://omim.org/entry/138040 138040]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref> <ref>PMID:1704018</ref> <ref>PMID:7683692</ref> <ref>PMID:11589680</ref> <ref>PMID:11701741</ref>
== Function ==
[https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/m2/1m2z_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1m2z ConSurf].
<div style="clear:both"></div>


===Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif===
==See Also==
 
*[[Glucocorticoid receptor|Glucocorticoid receptor]]
 
*[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]]
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== References ==
The line below this paragraph, {{ABSTRACT_PUBMED_12151000}}, adds the Publication Abstract to the page
<references/>
(as it appears on PubMed at http://www.pubmed.gov), where 12151000 is the PubMed ID number.
__TOC__
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</StructureSection>
{{ABSTRACT_PUBMED_12151000}}
 
==About this Structure==
1M2Z is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M2Z OCA].
 
==Reference==
Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition., Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM, Lambert MH, Moore JT, Pearce KH, Xu HE, Cell. 2002 Jul 12;110(1):93-105. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12151000 12151000]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Apolito, C J.]]
[[Category: Apolito CJ]]
[[Category: Bledsoe, R B.]]
[[Category: Bledsoe RB]]
[[Category: Consler, T G.]]
[[Category: Consler TG]]
[[Category: Delves, C J.]]
[[Category: Delves CJ]]
[[Category: Lambert, M H.]]
[[Category: Lambert MH]]
[[Category: Mckee, D D.]]
[[Category: Mckee DD]]
[[Category: Montana, V G.]]
[[Category: Montana VG]]
[[Category: Moore, J T.]]
[[Category: Moore JT]]
[[Category: Parks, D J.]]
[[Category: Parks DJ]]
[[Category: Pearce, K H.]]
[[Category: Pearce KH]]
[[Category: Stanley, T B.]]
[[Category: Stanley TB]]
[[Category: Stewart, E L.]]
[[Category: Stewart EL]]
[[Category: Willson, T M.]]
[[Category: Willson TM]]
[[Category: Xu, H E.]]
[[Category: Xu HE]]
[[Category: Charge clamp]]
[[Category: Coactivator]]
[[Category: Dexamethasone]]
[[Category: Dimer interface]]
[[Category: Glucocorticoid receptor]]
[[Category: Hormone binding pocket]]
[[Category: Tif2]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul  2 23:06:24 2008''

Latest revision as of 10:39, 14 February 2024

Crystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motifCrystal structure of a dimer complex of the human glucocorticoid receptor ligand-binding domain bound to dexamethasone and a TIF2 coactivator motif

Structural highlights

1m2z is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

GCR_HUMAN Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:138040; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.[1] [2] [3] [4] [5]

Function

GCR_HUMAN Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Vottero A, Kino T, Combe H, Lecomte P, Chrousos GP. A novel, C-terminal dominant negative mutation of the GR causes familial glucocorticoid resistance through abnormal interactions with p160 steroid receptor coactivators. J Clin Endocrinol Metab. 2002 Jun;87(6):2658-67. PMID:12050230
  2. ↑ Hurley DM, Accili D, Stratakis CA, Karl M, Vamvakopoulos N, Rorer E, Constantine K, Taylor SI, Chrousos GP. Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest. 1991 Feb;87(2):680-6. PMID:1704018 doi:http://dx.doi.org/10.1172/JCI115046
  3. ↑ Malchoff DM, Brufsky A, Reardon G, McDermott P, Javier EC, Bergh CH, Rowe D, Malchoff CD. A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest. 1993 May;91(5):1918-25. PMID:7683692 doi:http://dx.doi.org/10.1172/JCI116410
  4. ↑ Ruiz M, Lind U, Gafvels M, Eggertsen G, Carlstedt-Duke J, Nilsson L, Holtmann M, Stierna P, Wikstrom AC, Werner S. Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol (Oxf). 2001 Sep;55(3):363-71. PMID:11589680
  5. ↑ Kino T, Stauber RH, Resau JH, Pavlakis GN, Chrousos GP. Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking. J Clin Endocrinol Metab. 2001 Nov;86(11):5600-8. PMID:11701741
  6. ↑ Psarra AM, Sekeris CE. Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: role of the mitochondrial glucocorticoid receptor. Biochim Biophys Acta. 2011 Oct;1813(10):1814-21. doi:, 10.1016/j.bbamcr.2011.05.014. Epub 2011 Jun 2. PMID:21664385 doi:10.1016/j.bbamcr.2011.05.014

1m2z, resolution 2.50Å

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