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.

2gpp

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:23, 20 June 2018

Estrogen Related Receptor-gamma ligand binding domain complexed with a RIP140 peptide and synthetic ligand GSK4716

Structural highlights

2gpp is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2gp7, 2gpo, 2gpu, 2gpv
Gene:	ESRRG (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ERR3_HUMAN] Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).^[1] ^[2] ^[3] [NRIP1_HUMAN] Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors.^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

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

X-ray crystal structures of the ligand binding domain (LBD) of the estrogen-related receptor-gamma (ERRgamma) were determined that describe this receptor in three distinct states: unliganded, inverse agonist bound, and agonist bound. Two structures were solved for the unliganded state, the ERRgamma LBD alone, and in complex with a coregulator peptide representing a portion of receptor interacting protein 140 (RIP140). No significant differences were seen between these structures that both exhibited the conformation of ERRgamma seen in studies with other coactivators. Two structures were obtained describing the inverse agonist-bound state, the ERRgamma LBD with 4-hydroxytamoxifen (4-OHT), and the ERRgamma LBD with 4-OHT and a peptide representing a portion of the silencing mediator of retinoid and thyroid hormone action protein (SMRT). The 4-OHT structure was similar to other reported inverse agonist bound structures, showing reorientation of phenylalanine 435 and a displacement of the AF-2 helix relative to the unliganded structures with little other rearrangement occurring. No significant changes to the LBD appear to be induced by peptide binding with the addition of the SMRT peptide to the ERRgamma plus 4-OHT complex. The observed agonist-bound state contains the ERRgamma LBD, a ligand (GSK4716), and the RIP140 peptide and reveals an unexpected rearrangement of the phenol-binding residues. Thermal stability studies show that agonist binding leads to global stabilization of the ligand binding domain. In contrast to the conventional mechanism of nuclear receptor ligand activation, activation of ERRgamma by GSK4716 does not appear to involve a major rearrangement or significant stabilization of the C-terminal helix.

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.,Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT J Biol Chem. 2006 Dec 8;281(49):37773-81. Epub 2006 Sep 21. PMID:16990259^[10]

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

References

↑ Hentschke M, Susens U, Borgmeyer U. Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases. Biochem J. 2009 Apr 1;419(1):167-76. doi: 10.1042/BJ20081556. PMID:19067653 doi:10.1042/BJ20081556
↑ Tremblay AM, Wilson BJ, Yang XJ, Giguere V. Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. PMID:18063693 doi:me.2007-0357
↑ Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP. Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell. 2002 Feb;9(2):303-13. PMID:11864604
↑ Cavailles V, Dauvois S, L'Horset F, Lopez G, Hoare S, Kushner PJ, Parker MG. Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor. EMBO J. 1995 Aug 1;14(15):3741-51. PMID:7641693
↑ Subramaniam N, Treuter E, Okret S. Receptor interacting protein RIP140 inhibits both positive and negative gene regulation by glucocorticoids. J Biol Chem. 1999 Jun 18;274(25):18121-7. PMID:10364267
↑ Vo N, Fjeld C, Goodman RH. Acetylation of nuclear hormone receptor-interacting protein RIP140 regulates binding of the transcriptional corepressor CtBP. Mol Cell Biol. 2001 Sep;21(18):6181-8. PMID:11509661
↑ Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombes M. A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action. Mol Endocrinol. 2001 Sep;15(9):1586-98. PMID:11518808
↑ Teyssier C, Belguise K, Galtier F, Cavailles V, Chalbos D. Receptor-interacting protein 140 binds c-Jun and inhibits estradiol-induced activator protein-1 activity by reversing glucocorticoid receptor-interacting protein 1 effect. Mol Endocrinol. 2003 Feb;17(2):287-99. PMID:12554755 doi:http://dx.doi.org/10.1210/me.2002-0324
↑ Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, Khochbin S, Jalaguier S, Cavailles V. Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition. Nucleic Acids Res. 2004 Apr 1;32(6):1957-66. Print 2004. PMID:15060175 doi:http://dx.doi.org/10.1093/nar/gkh524
↑ 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

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/2gpp"

@@ Line 1: / Line 1: @@
 ==Estrogen Related Receptor-gamma ligand binding domain complexed with a RIP140 peptide and synthetic ligand GSK4716==
 <StructureSection load='2gpp' size='340' side='right' caption='[[2gpp]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gp7|2gp7]], [[2gpo|2gpo]], [[2gpu|2gpu]], [[2gpv|2gpv]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ESRRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<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=2gpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gpp OCA], [http://pdbe.org/2gpp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gpp RCSB], [http://www.ebi.ac.uk/pdbsum/2gpp PDBsum]</span></td></tr>
+<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=2gpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gpp OCA], [http://pdbe.org/2gpp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gpp RCSB], [http://www.ebi.ac.uk/pdbsum/2gpp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gpp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/2gpp_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/2gpp_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2gpp ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2gpp

From Proteopedia

Revision as of 07:23, 20 June 2018

Estrogen Related Receptor-gamma ligand binding domain complexed with a RIP140 peptide and synthetic ligand GSK4716

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