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New page: left|200px<br /> <applet load="1zdu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zdu, resolution 2.50Å" /> '''The Crystal Structu...
 
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[[Image:1zdu.gif|left|200px]]<br />
<applet load="1zdu" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1zdu, resolution 2.50&Aring;" />
'''The Crystal Structure of Human Liver Receptor Homologue-1'''<br />


==Overview==
==The Crystal Structure of Human Liver Receptor Homologue-1==
Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1), belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1, is an essential factor for sex determination during development and, regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1, is a critical factor for development of endodermal tissues and regulates, cholesterol and bile acid homeostasis. Regulatory ligands are unknown for, SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket, in a region commonly occupied by ligands in the structures of other, nuclear receptors, and pocket-filling mutations did not alter the, constitutive activity observed. Here we report the crystal structures of, the putative ligand-binding domains of human SF-1 at 2.1-A resolution and, human LRH-1 at 2.5-A resolution. Both structures bind a, coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human, LRH-1, coactivator peptide binding also occurs to a second site. We, discovered in both structures a phospholipid molecule bound in a pocket of, the putative ligand-binding domain. MS analysis of the protein samples, used for crystallization indicated that the two proteins associate with a, range of phospholipids. Mutations of the pocket-lining residues reduced, the transcriptional activities of SF-1 and LRH-1 in mammalian cell, transfection assays without affecting their expression levels. These, results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other, molecules regulate SF-1 or LRH-1 under physiological conditions.
<StructureSection load='1zdu' size='340' side='right'caption='[[1zdu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zdu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZDU 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3A:PHOSPHATIDYLGLYCEROL-PHOSPHOGLYCEROL'>P3A</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=1zdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdu OCA], [https://pdbe.org/1zdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdu RCSB], [https://www.ebi.ac.uk/pdbsum/1zdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development.
== 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/zd/1zdu_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=1zdu ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ZDU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with P3A and TRS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZDU OCA].
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
 
__TOC__
==Reference==
</StructureSection>
The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1., Wang W, Zhang C, Marimuthu A, Krupka HI, Tabrizizad M, Shelloe R, Mehra U, Eng K, Nguyen H, Settachatgul C, Powell B, Milburn MV, West BL, Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. Epub 2005 May 16. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15897460 15897460]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Eng, K.]]
[[Category: Eng K]]
[[Category: Krupka, H.I.]]
[[Category: Krupka HI]]
[[Category: Marimuthu, A.]]
[[Category: Marimuthu A]]
[[Category: Mehra, U.]]
[[Category: Mehra U]]
[[Category: Milburn, M.V.]]
[[Category: Milburn MV]]
[[Category: Nguyen, H.]]
[[Category: Nguyen H]]
[[Category: Powell, B.]]
[[Category: Powell B]]
[[Category: Settachatgul, C.]]
[[Category: Settachatgul C]]
[[Category: Shelloe, R.]]
[[Category: Shelloe R]]
[[Category: Tabrizizad, M.]]
[[Category: Tabrizizad M]]
[[Category: Wang, W.]]
[[Category: Wang W]]
[[Category: West, B.L.]]
[[Category: West BL]]
[[Category: Zhang, C.]]
[[Category: Zhang C]]
[[Category: P3A]]
[[Category: TRS]]
[[Category: liver receptor homologue-1]]
[[Category: lrh-1]]
[[Category: nuclear receptor]]
[[Category: phosphatidylethanolamine]]
[[Category: phospholipid]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:33:03 2007''

Latest revision as of 09:03, 14 February 2024

The Crystal Structure of Human Liver Receptor Homologue-1

1zdu, resolution 2.50Å

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