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| | ==STRUCTURE REFINEMENT OF THE GLUCOCORTICOID RECEPTOR-DNA BINDING DOMAIN FROM NMR DATA BY RELAXATION MATRIX CALCULATIONS== | | ==STRUCTURE REFINEMENT OF THE GLUCOCORTICOID RECEPTOR-DNA BINDING DOMAIN FROM NMR DATA BY RELAXATION MATRIX CALCULATIONS== |
| - | <StructureSection load='1rgd' size='340' side='right'caption='[[1rgd]], [[NMR_Ensembles_of_Models | 11 NMR models]]' scene=''> | + | <StructureSection load='1rgd' size='340' side='right'caption='[[1rgd]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1rgd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RGD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1rgd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RGD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RGD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgd OCA], [https://pdbe.org/1rgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rgd RCSB], [https://www.ebi.ac.uk/pdbsum/1rgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rgd ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rgd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rgd OCA], [https://pdbe.org/1rgd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rgd RCSB], [https://www.ebi.ac.uk/pdbsum/1rgd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rgd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GCR_RAT GCR_RAT]] 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 (By similarity).<ref>PMID:12917342</ref>
| + | [https://www.uniprot.org/uniprot/GCR_RAT GCR_RAT] 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 (By similarity).<ref>PMID:12917342</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Boelens, R]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Bonvin, A M.J J]] | + | [[Category: Boelens R]] |
| - | [[Category: Davis, A]] | + | [[Category: Bonvin AMJJ]] |
| - | [[Category: Hard, K]] | + | [[Category: Davis A]] |
| - | [[Category: Kaptein, R]] | + | [[Category: Hard K]] |
| - | [[Category: Maler, B]] | + | [[Category: Kaptein R]] |
| - | [[Category: Tilborg, M A.A Van]] | + | [[Category: Maler B]] |
| - | [[Category: Yamamoto, K R]] | + | [[Category: Van Tilborg MAA]] |
| - | [[Category: Dna-binding protein]]
| + | [[Category: Yamamoto KR]] |
| Structural highlights
Function
GCR_RAT 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 (By similarity).[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The solution structure of the glucocorticoid receptor (GR) DNA-binding domain (DBD), consisting of 93 residues, has been refined from two and three-dimensional NMR data using an ensemble iterative relaxation matrix approach followed by direct NOE refinement with DINOSAUR. A set of 47 structures of the rat GR fragment Cys440-Arg510 was generated with distance geometry and further refined with a combination of restrained energy minimization and restrained molecular dynamics in a parallel refinement protocol. Distance constraints were obtained from an extensive set of NOE build-up curves in H2O and 2H2O via relaxation matrix calculations (1186 distance constraints from NOE intensities, 10 phi and 22 chi 1 dihedral angle constraints from J- coupling data were used for the calculations). The root-mean-square deviation values of the 11 best structures on the well-determined part of the protein (Cys440 to Ser448, His451 to Glu469 and Pro493 to Glu508) are 0.60 A and 1.20 A from the average for backbone and all heavy atoms, respectively. The final structures have R-factors around 0.40 and good stereochemical qualities. The first zinc-coordinating domain of the GR DBD is very similar to the crystal structure with a root-mean-square difference of 1.4 A. The second zinc-coordinating domain is still disordered in solution. No secondary structure element is found in this domain in the free state. As suggested by crystallographic studies on the estrogen receptor DBD-DNA and GR DBD-DNA complexes, part of this region will form a distorted helix and the D-box will undergo a conformational change upon cooperative binding to DNA.
Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations.,van Tilborg MA, Bonvin AM, Hard K, Davis AL, Maler B, Boelens R, Yamamoto KR, Kaptein R J Mol Biol. 1995 Apr 7;247(4):689-700. PMID:7723024[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK. BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol Cell Biol. 2003 Sep;23(17):6210-20. PMID:12917342
- ↑ van Tilborg MA, Bonvin AM, Hard K, Davis AL, Maler B, Boelens R, Yamamoto KR, Kaptein R. Structure refinement of the glucocorticoid receptor-DNA binding domain from NMR data by relaxation matrix calculations. J Mol Biol. 1995 Apr 7;247(4):689-700. PMID:7723024 doi:http://dx.doi.org/10.1006/jmbi.1995.0173
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