2uzk: Difference between revisions

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{{Seed}}
[[Image:2uzk.png|left|200px]]


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==Crystal structure of the human FOXO3a-DBD bound to DNA==
The line below this paragraph, containing "STRUCTURE_2uzk", creates the "Structure Box" on the page.
<StructureSection load='2uzk' size='340' side='right'caption='[[2uzk]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2uzk]] is a 6 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=2UZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZK FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#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=2uzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzk OCA], [https://pdbe.org/2uzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uzk RCSB], [https://www.ebi.ac.uk/pdbsum/2uzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uzk ProSAT]</span></td></tr>
{{STRUCTURE_2uzk|  PDB=2uzk  |  SCENE=  }}
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FOXO3_HUMAN FOXO3_HUMAN] Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with MLL/HRX.
== Function ==
[https://www.uniprot.org/uniprot/FOXO3_HUMAN FOXO3_HUMAN] Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation.<ref>PMID:10102273</ref> <ref>PMID:16751106</ref> <ref>PMID:21329882</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/uz/2uzk_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=2uzk ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
FOXO3a is a transcription factor of the FOXO family. The FOXO proteins participate in multiple signaling pathways, and their transcriptional activity is regulated by several post-translational mechanisms, including phosphorylation, acetylation and ubiquitination. Because these post-translational modification sites are located within the C-terminal basic region of the FOXO DNA-binding domain (FOXO-DBD), it is possible that these post-translational modifications could alter the DNA-binding characteristics. To understand how FOXO mediate transcriptional activity, we report here the 2.7 A crystal structure of the DNA-binding domain of FOXO3a (FOXO3a-DBD) bound to a 13-bp DNA duplex containing a FOXO consensus binding sequence (GTAAACA). Based on a unique structural feature in the C-terminal region and results from biochemical and mutational studies, our studies may explain how FOXO-DBD C-terminal phosphorylation by protein kinase B (PKB) or acetylation by cAMP-response element binding protein (CBP) can attenuate the DNA-binding activity and thereby reduce transcriptional activity of FOXO proteins. In addition, we demonstrate that the methyl groups of specific thymine bases within the consensus sequence are important for FOXO3a-DBD recognition of the consensus binding site.


===CRYSTAL STRUCTURE OF THE HUMAN FOXO3A-DBD BOUND TO DNA===
Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification.,Tsai KL, Sun YJ, Huang CY, Yang JY, Hung MC, Hsiao CD Nucleic Acids Res. 2007;35(20):6984-94. Epub 2007 Oct 16. PMID:17940099<ref>PMID:17940099</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2uzk" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
2UZK is a 6 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZK OCA].
*[[FOX 3D structures|FOX 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Hsiao, C D.]]
[[Category: Large Structures]]
[[Category: Huang, C Y.]]
[[Category: Hsiao C-D]]
[[Category: Hung, M C.]]
[[Category: Huang C-Y]]
[[Category: Sun, Y J.]]
[[Category: Hung M-C]]
[[Category: Tsai, K L.]]
[[Category: Sun Y-J]]
[[Category: Yang, J Y.]]
[[Category: Tsai K-L]]
[[Category: Activator]]
[[Category: Yang J-Y]]
[[Category: Apoptosis]]
[[Category: Chromosomal rearrangement]]
[[Category: Dna-binding]]
[[Category: Dna-binding domain]]
[[Category: Forkhead]]
[[Category: Forkhead transcription factor]]
[[Category: Foxo]]
[[Category: Nuclear protein]]
[[Category: Phosphorylation]]
[[Category: Proto-oncogene]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Winged helix]]
 
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Retrieved from "https://proteopedia.org/2uzk"