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[[Image:1pk5.gif|left|200px]]
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{{STRUCTURE_1pk5|  PDB=1pk5  |  SCENE=  }}
'''Crystal structure of the orphan nuclear receptor LRH-1'''


==Crystal structure of the orphan nuclear receptor LRH-1==
<StructureSection load='1pk5' size='340' side='right'caption='[[1pk5]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pk5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PK5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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=1pk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pk5 OCA], [https://pdbe.org/1pk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pk5 RCSB], [https://www.ebi.ac.uk/pdbsum/1pk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pk5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NR5A2_MOUSE NR5A2_MOUSE] Binds to promoters containing the sequence element 5'-AACGACCGACCTTGAG-3'. Plays a role in the regulation of gene expression in liver and pancreas. May play a role in embryonic development (By similarity).
== 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/pk/1pk5_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=1pk5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The orphan nuclear receptors SF-1 and LRH-1 are constitutively active, but it remains uncertain whether their activation is hormone dependent. We report the crystal structure of the LRH-1 ligand binding domain to 2.4 A resolution and find the receptor to be a monomer that adopts an active conformation with a large but empty hydrophobic pocket. Adding bulky side chains into this pocket resulted in full or greater activity suggesting that, while LRH-1 could accommodate potential ligands, these are dispensable for basal activity. Constitutive LRH-1 activity appears to be conferred by a distinct structural element consisting of an extended helix 2 that provides an additional layer to the canonical LBD fold. Mutating the conserved arginine in helix 2 reduced LRH-1 receptor activity and coregulator recruitment, consistent with the partial loss-of-function phenotype exhibited by an analogous SF-1 human mutant. These findings illustrate an alternative structural strategy for nuclear receptor stabilization in the absence of ligand binding.


==Overview==
Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1.,Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA Mol Cell. 2003 Jun;11(6):1575-85. PMID:12820970<ref>PMID:12820970</ref>
The orphan nuclear receptors SF-1 and LRH-1 are constitutively active, but it remains uncertain whether their activation is hormone dependent. We report the crystal structure of the LRH-1 ligand binding domain to 2.4 A resolution and find the receptor to be a monomer that adopts an active conformation with a large but empty hydrophobic pocket. Adding bulky side chains into this pocket resulted in full or greater activity suggesting that, while LRH-1 could accommodate potential ligands, these are dispensable for basal activity. Constitutive LRH-1 activity appears to be conferred by a distinct structural element consisting of an extended helix 2 that provides an additional layer to the canonical LBD fold. Mutating the conserved arginine in helix 2 reduced LRH-1 receptor activity and coregulator recruitment, consistent with the partial loss-of-function phenotype exhibited by an analogous SF-1 human mutant. These findings illustrate an alternative structural strategy for nuclear receptor stabilization in the absence of ligand binding.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1PK5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PK5 OCA].
</div>
<div class="pdbe-citations 1pk5" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1., Sablin EP, Krylova IN, Fletterick RJ, Ingraham HA, Mol Cell. 2003 Jun;11(6):1575-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12820970 12820970]
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Fletterick RJ]]
[[Category: Fletterick, R J.]]
[[Category: Ingraham HA]]
[[Category: Ingraham, H A.]]
[[Category: Krylova IN]]
[[Category: Krylova, I N.]]
[[Category: Sablin EP]]
[[Category: Sablin, E P.]]
[[Category: Ligand-binding domain]]
[[Category: Lrh-1]]
[[Category: Nuclear receptor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:10:52 2008''

Latest revision as of 09:44, 16 August 2023

Crystal structure of the orphan nuclear receptor LRH-1

1pk5, resolution 2.40Å

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