3l2c

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[[Image:3l2c.png|left|200px]]
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==Crystal Structure of the DNA Binding Domain of FOXO4 Bound to DNA==
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<StructureSection load='3l2c' size='340' side='right' caption='[[3l2c]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3l2c]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bpy 3bpy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L2C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L2C FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFX, AFX1, FOXO4, MLLT7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l2c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l2c RCSB], [http://www.ebi.ac.uk/pdbsum/3l2c PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FOXO4_HUMAN FOXO4_HUMAN]] A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with KMT2A/MLL1. The result is a rogue activator protein.
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== Function ==
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[[http://www.uniprot.org/uniprot/FOXO4_HUMAN FOXO4_HUMAN]] Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity.<ref>PMID:10217147</ref> <ref>PMID:10783894</ref> <ref>PMID:12761217</ref> <ref>PMID:15126506</ref> <ref>PMID:16054032</ref> <ref>PMID:16964248</ref> <ref>PMID:20874444</ref> <ref>PMID:22972301</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l2/3l2c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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FOXO4 is a member of the FOXO subgroup of forkhead transcription factors that constitute key components of a conserved signalling pathway that connects growth and stress signals to transcriptional control. Here, the 1.9 A resolution crystal structure of the DNA-binding domain of human FOXO4 (FOXO4-DBD) bound to a 13 bp DNA duplex containing a FOXO consensus binding sequence is reported. The structure shows a similar recognition of the core sequence as has been shown for two other FOXO proteins. Helix H3 is docked into the major groove and provides all of the base-specific contacts, while the N-terminus and wing W1 make additional contacts with the phosphate groups of DNA. In contrast to other FOXO-DBD-DNA structures, the loop between helices H2 and H3 has a different conformation and participates in DNA binding. In addition, the structure of the FOXO4-DBD-DNA complex suggests that both direct water-DNA base contacts and the unique water-network interactions contribute to FOXO-DBD binding to the DNA in a sequence-specific manner.
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{{STRUCTURE_3l2c| PDB=3l2c | SCENE= }}
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Structure of the human FOXO4-DBD-DNA complex at 1.9 A resolution reveals new details of FOXO binding to the DNA.,Boura E, Rezabkova L, Brynda J, Obsilova V, Obsil T Acta Crystallogr D Biol Crystallogr. 2010 Dec;66(Pt 12):1351-7. Epub 2010, Nov 16. PMID:21123876<ref>PMID:21123876</ref>
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===Crystal Structure of the DNA Binding Domain of FOXO4 Bound to DNA===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_21123876}}
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==About this Structure==
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[[3l2c]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bpy 3bpy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L2C OCA].
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==See Also==
==See Also==
*[[Forkhead box protein|Forkhead box protein]]
*[[Forkhead box protein|Forkhead box protein]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021123876</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Boura, E.]]
[[Category: Boura, E.]]

Revision as of 12:56, 29 September 2014

Crystal Structure of the DNA Binding Domain of FOXO4 Bound to DNA

3l2c, resolution 1.87Å

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