2uzk
From Proteopedia
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| - | [[Image:2uzk.png|left|200px]] | ||
| - | + | ==Crystal structure of the human FOXO3a-DBD bound to DNA== | |
| + | <StructureSection load='2uzk' size='340' side='right'caption='[[2uzk]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <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> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</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> | ||
| + | </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/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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2uzk" style="background-color:#fffaf0;"></div> | |
==See Also== | ==See Also== | ||
| - | *[[ | + | *[[FOX 3D structures|FOX 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Hsiao | + | [[Category: Large Structures]] |
| - | [[Category: Huang | + | [[Category: Hsiao C-D]] |
| - | [[Category: Hung | + | [[Category: Huang C-Y]] |
| - | [[Category: Sun | + | [[Category: Hung M-C]] |
| - | [[Category: Tsai | + | [[Category: Sun Y-J]] |
| - | [[Category: Yang | + | [[Category: Tsai K-L]] |
| - | + | [[Category: Yang J-Y]] | |
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Current revision
Crystal structure of the human FOXO3a-DBD bound to DNA
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Categories: Homo sapiens | Large Structures | Hsiao C-D | Huang C-Y | Hung M-C | Sun Y-J | Tsai K-L | Yang J-Y
