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New page: left|200px<br /><applet load="1t76" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t76, resolution 2.10Å" /> '''Crystal structure of...
 
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[[Image:1t76.jpg|left|200px]]<br /><applet load="1t76" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1t76, resolution 2.10&Aring;" />
'''Crystal structure of the androgen receptor ligand binding domain in complex with a WxxVW motif'''<br />


==Overview==
==Crystal structure of the androgen receptor ligand binding domain in complex with a WxxVW motif==
Prostate cancer is a leading killer of men in the industrialized world., Underlying this disease is the aberrant action of the androgen receptor, (AR). AR is distinguished from other nuclear receptors in that after, hormone binding, it preferentially responds to a specialized set of, coactivators bearing aromatic-rich motifs, while responding poorly to, coactivators bearing the leucine-rich "NR box" motifs favored by other, nuclear receptors. Under normal conditions, interactions with these, AR-specific coactivators through aromatic-rich motifs underlie targeted, gene transcription. However, during prostate cancer, abnormal association, with such coactivators, as well as with coactivators containing canonical, leucine-rich motifs, promotes disease progression. To understand the, paradox of this unusual selectivity, we have derived a complete set of, peptide motifs that interact with AR using phage display. Binding, affinities were measured for a selected set of these peptides and their, interactions with AR determined by X-ray crystallography. Structures of AR, in complex with FxxLF, LxxLL, FxxLW, WxxLF, WxxVW, FxxFF, and FxxYF motifs, reveal a changing surface of the AR coactivator binding interface that, permits accommodation of both AR-specific aromatic-rich motifs and, canonical leucine-rich motifs. Induced fit provides perfect mating of the, motifs representing the known family of AR coactivators and suggests a, framework for the design of AR coactivator antagonists.
<StructureSection load='1t76' size='340' side='right'caption='[[1t76]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1t76]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pan_troglodytes Pan troglodytes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T76 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1t76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t76 OCA], [https://pdbe.org/1t76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t76 RCSB], [https://www.ebi.ac.uk/pdbsum/1t76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t76 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ANDR_PANTR ANDR_PANTR] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2.Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (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/t7/1t76_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=1t76 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1T76 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pan_troglodytes Pan troglodytes] with SO4, NA, DHT and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1T76 OCA].
*[[Androgen receptor 3D structures|Androgen receptor 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Recognition and accommodation at the androgen receptor coactivator binding interface., Hur E, Pfaff SJ, Payne ES, Gron H, Buehrer BM, Fletterick RJ, PLoS Biol. 2004 Sep;2(9):E274. Epub 2004 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15328534 15328534]
[[Category: Large Structures]]
[[Category: Pan troglodytes]]
[[Category: Pan troglodytes]]
[[Category: Single protein]]
[[Category: Buehrer BM]]
[[Category: Buehrer, B.M.]]
[[Category: Fletterick RJ]]
[[Category: Fletterick, R.J.]]
[[Category: Gron H]]
[[Category: Gron, H.]]
[[Category: Hur E]]
[[Category: Hur, E.]]
[[Category: Payne ES]]
[[Category: Payne, E.S.]]
[[Category: Pfaff SJ]]
[[Category: Pfaff, S.J.]]
[[Category: DHT]]
[[Category: EDO]]
[[Category: NA]]
[[Category: SO4]]
[[Category: af-2]]
[[Category: alpha-helical sandwich]]
[[Category: androgen]]
[[Category: dht]]
[[Category: ligand binding domain]]
[[Category: nuclear receptor]]
[[Category: testosterone]]
[[Category: transcription factor]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:02:22 2007''

Latest revision as of 08:36, 14 February 2024

Crystal structure of the androgen receptor ligand binding domain in complex with a WxxVW motif

1t76, resolution 2.10Å

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