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New page: left|200px<br /> <applet load="1yok" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yok, resolution 2.5Å" /> '''crystal structure of...
 
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[[Image:1yok.gif|left|200px]]<br />
<applet load="1yok" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1yok, resolution 2.5&Aring;" />
'''crystal structure of human LRH-1 bound with TIF-2 peptide and phosphatidylglycerol'''<br />


==Overview==
==crystal structure of human LRH-1 bound with TIF-2 peptide and phosphatidylglycerol==
Vertebrate members of the nuclear receptor NR5A subfamily, which includes, steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1), regulate crucial aspects of development, endocrine homeostasis, and, metabolism. Mouse LRH-1 is believed to be a ligand-independent, transcription factor with a large and empty hydrophobic pocket. Here we, present structural and biochemical data for three other NR5A members-mouse, and human SF-1 and human LRH-1-which reveal that these receptors bind, phosphatidyl inositol second messengers and that ligand binding is, required for maximal activity. Evolutionary analysis of structure-function, relationships across the SF-1/LRH-1 subfamily indicates that ligand, binding is the ancestral state of NR5A receptors and was uniquely, diminished or altered in the rodent LRH-1 lineage. We propose that, phospholipids regulate gene expression by directly binding to NR5A nuclear, receptors.
<StructureSection load='1yok' size='340' side='right'caption='[[1yok]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1yok]] 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=1YOK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YOK 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=P6L:(2S)-3-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-2-[(6E)-HEXADEC-6-ENOYLOXY]PROPYL+(8E)-OCTADEC-8-ENOATE'>P6L</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=1yok FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yok OCA], [https://pdbe.org/1yok PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yok RCSB], [https://www.ebi.ac.uk/pdbsum/1yok PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yok ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
== Function ==
[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] 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:9430642</ref>
== 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/yo/1yok_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=1yok ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1YOK 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 P6L as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YOK OCA].
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
 
== References ==
==Reference==
<references/>
Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1., Krylova IN, Sablin EP, Moore J, Xu RX, Waitt GM, MacKay JA, Juzumiene D, Bynum JM, Madauss K, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ, Willson TM, Ingraham HA, Cell. 2005 Feb 11;120(3):343-55. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15707893 15707893]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Bynum, J.M.]]
[[Category: Bynum JM]]
[[Category: Fletterick, R.J.]]
[[Category: Fletterick RJ]]
[[Category: Guy, R.K.]]
[[Category: Guy RK]]
[[Category: Ingraham, H.A.]]
[[Category: Ingraham HA]]
[[Category: Juzumiene, D.]]
[[Category: Juzumiene D]]
[[Category: Krylova, I.N.]]
[[Category: Krylova IN]]
[[Category: Lebedeva, L.]]
[[Category: Lebedeva L]]
[[Category: MacKay, J.A.]]
[[Category: MacKay JA]]
[[Category: Madauss, K.]]
[[Category: Madauss K]]
[[Category: Montana, V.]]
[[Category: Montana V]]
[[Category: Moore, J.]]
[[Category: Moore J]]
[[Category: Sablin, E.P.]]
[[Category: Sablin EP]]
[[Category: Suzawa, M.]]
[[Category: Suzawa M]]
[[Category: Thornton, J.W.]]
[[Category: Thornton JW]]
[[Category: Waitt, G.M.]]
[[Category: Waitt GM]]
[[Category: Williams, J.D.]]
[[Category: Williams JD]]
[[Category: Williams, S.P.]]
[[Category: Williams SP]]
[[Category: Willson, T.M.]]
[[Category: Willson TM]]
[[Category: Xu, R.X.]]
[[Category: Xu RX]]
[[Category: P6L]]
[[Category: lrh-1]]
[[Category: phosphatidylglycerol]]
[[Category: tif-1]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:22:19 2007''

Latest revision as of 08:58, 14 February 2024

crystal structure of human LRH-1 bound with TIF-2 peptide and phosphatidylglycerol

1yok, resolution 2.50Å

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