3coa

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{{STRUCTURE_3coa| PDB=3coa | SCENE= }}
 
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===Crystal Structure of FoxO1 DBD Bound to IRE DNA===
 
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{{ABSTRACT_PUBMED_18786403}}
 
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==Disease==
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==Crystal Structure of FoxO1 DBD Bound to IRE DNA==
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[[http://www.uniprot.org/uniprot/FOXO1_HUMAN FOXO1_HUMAN]] Defects in FOXO1 are a cause of rhabdomyosarcoma type 2 (RMS2) [MIM:[http://omim.org/entry/268220 268220]]. It is a form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchimal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=Chromosomal aberrations involving FOXO1 are found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3 and translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator.
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<StructureSection load='3coa' size='340' side='right'caption='[[3coa]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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==Function==
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<table><tr><td colspan='2'>[[3coa]] 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=3COA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3COA FirstGlance]. <br>
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[[http://www.uniprot.org/uniprot/FOXO1_HUMAN FOXO1_HUMAN]] Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts syngernistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A to activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose. Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells.<ref>PMID:10358076</ref><ref>PMID:12228231</ref><ref>PMID:15220471</ref><ref>PMID:15890677</ref><ref>PMID:18356527</ref><ref>PMID:19221179</ref><ref>PMID:21245099</ref>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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==About this Structure==
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3coa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3coa OCA], [https://pdbe.org/3coa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3coa RCSB], [https://www.ebi.ac.uk/pdbsum/3coa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3coa ProSAT]</span></td></tr>
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[[3coa]] is a 6 chain structure with sequence 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=3COA OCA].
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FOXO1_HUMAN FOXO1_HUMAN] Defects in FOXO1 are a cause of rhabdomyosarcoma type 2 (RMS2) [MIM:[https://omim.org/entry/268220 268220]. It is a form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchimal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. Note=Chromosomal aberrations involving FOXO1 are found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3 and translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator.
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== Function ==
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[https://www.uniprot.org/uniprot/FOXO1_HUMAN FOXO1_HUMAN] Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts syngernistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A to activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose. Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells.<ref>PMID:10358076</ref> <ref>PMID:12228231</ref> <ref>PMID:15220471</ref> <ref>PMID:15890677</ref> <ref>PMID:18356527</ref> <ref>PMID:19221179</ref> <ref>PMID:21245099</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/co/3coa_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/main_output.php?pdb_ID=3coa ConSurf].
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<div style="clear:both"></div>
==See Also==
==See Also==
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*[[Forkhead box protein|Forkhead box protein]]
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*[[FOX 3D structures|FOX 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018786403</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Anand, R.]]
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[[Category: Large Structures]]
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[[Category: Brent, M M.]]
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[[Category: Anand R]]
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[[Category: Marmorstein, R.]]
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[[Category: Brent MM]]
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[[Category: Dna-binding]]
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[[Category: Marmorstein R]]
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[[Category: Forkhead domain]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Proto-oncogene]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Transcription-dna complex]]
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[[Category: Winged helix]]
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Current revision

Crystal Structure of FoxO1 DBD Bound to IRE DNA

PDB ID 3coa

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