This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3mno

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 04:13, 25 December 2014

Crystal structure of the agonist form of mouse glucocorticoid receptor stabilized by (A611V, F608S) mutations at 1.55A

Structural highlights

3mno is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3mne, 3mnp
Gene:	Nr3c1, Grl, Grl1 (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GCR_MOUSE] 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. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.^[1] [NCOA2_MOUSE] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.^[2] ^[3]

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 human glucocorticoid receptor ligand-binding domain (hGR-LBD) is an important drug target for the treatment of various diseases. However, the low intrinsic stability and solubility of hGR-LBD have rendered its purification and biophysical characterization difficult. In order to overcome these problems, we have stabilized hGR-LBD by a combination of random mutagenesis and high-throughput screening using fluorescence-activated cell sorting (FACS) with enhanced green fluorescent protein (eGFP) as folding reporter. Two plasmid-encoded gene libraries of hGR-LBD fused to the egfp gene were expressed in Escherichia coli, followed by eight rounds of FACS screening, in each of which 10(8) cells were analyzed. The hgr-lbd mutants isolated by this approach contained numerous amino acid exchanges, and four beneficial ones (A605V, V702A, E705G, and M752T) were followed up in detail. Their characterization showed that the fluorescence of hGR-LBD-eGFP fusions is correlated linearly with the stability and solubility of hGR-LBD in the absence of eGFP. When combined, the four exchanges increased the thermal stability of hGR-LBD by more than 8 degrees C and enhanced its purification yield after expression in E. coli by about 26-fold. The introduction of three beneficial exchanges into the homologous ligand-binding domain of mouse enabled its X-ray structure determination at high resolution, which showed how the exchanges stabilize the protein and revealed atomic details that will guide future drug design. Our results demonstrate that large eGFP fusion libraries can be screened by FACS with extreme sensitivity and efficiency, yielding stabilized eukaryotic proteins suitable for biophysical characterization and structure determination.

Enhancing the stability and solubility of the glucocorticoid receptor ligand-binding domain by high-throughput library screening.,Seitz T, Thoma R, Schoch GA, Stihle M, Benz J, D'Arcy B, Wiget A, Ruf A, Hennig M, Sterner R J Mol Biol. 2010 Nov 5;403(4):562-77. Epub 2010 Sep 17. PMID:20850457^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hinds TD Jr, Stechschulte LA, Cash HA, Whisler D, Banerjee A, Yong W, Khuder SS, Kaw MK, Shou W, Najjar SM, Sanchez ER. Protein phosphatase 5 mediates lipid metabolism through reciprocal control of glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma (PPARgamma). J Biol Chem. 2011 Dec 16;286(50):42911-22. doi: 10.1074/jbc.M111.311662. Epub, 2011 Oct 12. PMID:21994940 doi:http://dx.doi.org/10.1074/jbc.M111.311662
↑ Picard F, Gehin M, Annicotte J, Rocchi S, Champy MF, O'Malley BW, Chambon P, Auwerx J. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell. 2002 Dec 27;111(7):931-41. PMID:12507421
↑ Lee YH, Koh SS, Zhang X, Cheng X, Stallcup MR. Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities. Mol Cell Biol. 2002 Jun;22(11):3621-32. PMID:11997499
↑ Seitz T, Thoma R, Schoch GA, Stihle M, Benz J, D'Arcy B, Wiget A, Ruf A, Hennig M, Sterner R. Enhancing the stability and solubility of the glucocorticoid receptor ligand-binding domain by high-throughput library screening. J Mol Biol. 2010 Nov 5;403(4):562-77. Epub 2010 Sep 17. PMID:20850457 doi:10.1016/j.jmb.2010.08.048

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mno"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mno OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mno RCSB], [http://www.ebi.ac.uk/pdbsum/3mno PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GCR_MOUSE GCR_MOUSE]] 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. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.<ref>PMID:21994940</ref>  [[http://www.uniprot.org/uniprot/NCOA2_MOUSE NCOA2_MOUSE]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:12507421</ref> <ref>PMID:11997499</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3mno

From Proteopedia

Revision as of 04:13, 25 December 2014

Crystal structure of the agonist form of mouse glucocorticoid receptor stabilized by (A611V, F608S) mutations at 1.55A

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox