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[[Image:2nxx.jpg|left|200px]]<br /><applet load="2nxx" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2nxx, resolution 2.750&Aring;" />
'''Crystal Structure of the Ligand-Binding Domains of the T.castaneum (Coleoptera) Heterodimer EcrUSP Bound to Ponasterone A'''<br />


==Overview==
==Crystal Structure of the Ligand-Binding Domains of the T.castaneum (Coleoptera) Heterodimer EcrUSP Bound to Ponasterone A==
Retinoid X receptor (RXR) and Ultraspiracle (USP) play a central role as ubiquitous heterodimerization partners of many nuclear receptors. While it has long been accepted that a wide range of ligands can activate vertebrate/mollusc RXRs, the existence and necessity of specific endogenous ligands activating RXR-USP in vivo is still matter of intense debate. Here we report the existence of a novel type of RXR-USP with a ligand-independent functional conformation. Our studies involved Tribolium USP (TcUSP) as representative of most arthropod RXR-USPs, with high sequence homology to vertebrate/mollusc RXRs. The crystal structure of the ligand-binding domain of TcUSP was solved in the context of the functional heterodimer with the ecdysone receptor (EcR). While EcR exhibits a canonical ligand-bound conformation, USP adopts an original apo structure. Our functional data demonstrate that TcUSP is a constitutively silent partner of EcR, and that none of the RXR ligands can bind and activate TcUSP. These findings together with a phylogenetic analysis suggest that RXR-USPs have undergone remarkable functional shifts during evolution and give insight into receptor-ligand binding evolution and dynamics.
<StructureSection load='2nxx' size='340' side='right'caption='[[2nxx]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[2nxx]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Tribolium_castaneum Tribolium castaneum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NXX FirstGlance]. <br>
2NXX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Tribolium_castaneum Tribolium castaneum] with <scene name='pdbligand=P1A:'>P1A</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NXX OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P1A:2,3,14,20,22-PENTAHYDROXYCHOLEST-7-EN-6-ONE'>P1A</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2nxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nxx OCA], [https://pdbe.org/2nxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nxx RCSB], [https://www.ebi.ac.uk/pdbsum/2nxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nxx ProSAT]</span></td></tr>
Structural and functional characterization of a novel type of ligand-independent RXR-USP receptor., Iwema T, Billas IM, Beck Y, Bonneton F, Nierengarten H, Chaumot A, Richards G, Laudet V, Moras D, EMBO J. 2007 Aug 22;26(16):3770-82. Epub 2007 Aug 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17673910 17673910]
</table>
[[Category: Protein complex]]
== Function ==
[https://www.uniprot.org/uniprot/A1JUG2_TRICA A1JUG2_TRICA]
== 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/nx/2nxx_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=2nxx ConSurf].
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Tribolium castaneum]]
[[Category: Tribolium castaneum]]
[[Category: Billas, I.]]
[[Category: Billas I]]
[[Category: Iwema, T.]]
[[Category: Iwema T]]
[[Category: Moras, D.]]
[[Category: Moras D]]
[[Category: P1A]]
[[Category: apo and holo ligand binding pocket]]
[[Category: hormone receptor]]
[[Category: hormone/growth factor complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:12:17 2008''

Latest revision as of 06:28, 3 April 2024

Crystal Structure of the Ligand-Binding Domains of the T.castaneum (Coleoptera) Heterodimer EcrUSP Bound to Ponasterone A

2nxx, resolution 2.75Å

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