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New page: left|200px<br /><applet load="1zh7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zh7, resolution 2.50Å" /> '''Structural and Bioch...
 
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[[Image:1zh7.gif|left|200px]]<br /><applet load="1zh7" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1zh7, resolution 2.50&Aring;" />
'''Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP'''<br />


==Overview==
==Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP==
The functional interaction between the orphan nuclear receptors small, heterodimer partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP, binds to LRH-1 and represses its constitutive transcriptional activity, is, crucial for regulating genes involved in cholesterol homeostasis. Here, we, report structural and biochemical analyses of the LRH-1/SHP interaction., The crystal structure and modeling studies of the LRH-1 ligand-binding, domain bound to either of the two LXXLL-related motifs of SHP show that, the receptor undergoes conformational changes to accommodate the SHP, docking and reveal key residues that determine the potency and selectivity, of SHP binding. Through a combination of mutagenesis and binding studies, we demonstrate that only the second SHP LXXLL motif is required for, repressing LRH-1, and this motif displays a strong preference for binding, to LRH-1 over the closely related receptor steroidogeneic factor 1 (SF-1)., Structural comparisons indicate that this binding selectivity is, determined by residues flanking the core LXXLL motifs. These results, establish a structural model for understanding how SHP interacts with, LRH-1 to regulate cholesterol homeostasis and provide new insights into, how nuclear receptor/coregulator selectivity is achieved.
<StructureSection load='1zh7' size='340' side='right'caption='[[1zh7]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zh7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZH7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZH7 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]] 2.5&#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=1zh7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zh7 OCA], [https://pdbe.org/1zh7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zh7 RCSB], [https://www.ebi.ac.uk/pdbsum/1zh7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zh7 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/zh/1zh7_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=1zh7 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ZH7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZH7 OCA].
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
 
__TOC__
==Reference==
</StructureSection>
Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner., Li Y, Choi M, Suino K, Kovach A, Daugherty J, Kliewer SA, Xu HE, Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9505-10. Epub 2005 Jun 23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15976031 15976031]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Choi, M.]]
[[Category: Choi M]]
[[Category: Daugherty, J.]]
[[Category: Daugherty J]]
[[Category: Kliewer, S.A.]]
[[Category: Kliewer SA]]
[[Category: Kovach, A.]]
[[Category: Kovach A]]
[[Category: Li, Y.]]
[[Category: Li Y]]
[[Category: Suino, K.]]
[[Category: Suino K]]
[[Category: Xu, H.E.]]
[[Category: Xu HE]]
[[Category: protein-peptide complex]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:27:10 2007''

Latest revision as of 09:04, 14 February 2024

Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP

1zh7, resolution 2.50Å

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