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| ==Crystal structure of the MafA homodimer bound to the consensus MARE== | | ==Crystal structure of the MafA homodimer bound to the consensus MARE== |
| <StructureSection load='4eot' size='340' side='right' caption='[[4eot]], [[Resolution|resolution]] 2.85Å' scene=''> | | <StructureSection load='4eot' size='340' side='right'caption='[[4eot]], [[Resolution|resolution]] 2.85Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4eot]] is a 4 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=4EOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EOT FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4eot]] is a 4 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=4EOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EOT FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.855Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eot RCSB], [http://www.ebi.ac.uk/pdbsum/4eot PDBsum]</span></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=4eot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eot OCA], [https://pdbe.org/4eot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eot RCSB], [https://www.ebi.ac.uk/pdbsum/4eot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eot ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/MAFA_HUMAN MAFA_HUMAN]] Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b and activates insulin gene expression. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.<ref>PMID:12011435</ref> <ref>PMID:12368292</ref> <ref>PMID:15665000</ref> <ref>PMID:15993959</ref> <ref>PMID:18042454</ref> <ref>PMID:19143053</ref> | | [https://www.uniprot.org/uniprot/MAFA_HUMAN MAFA_HUMAN] Acts as a transcriptional factor. Specifically binds the insulin enhancer element RIPE3b and activates insulin gene expression. Cooperates synergistically with NEUROD1 and PDX1. Phosphorylation by GSK3 increases its transcriptional activity and is required for its oncogenic activity. Involved either as an oncogene or as a tumor suppressor, depending on the cell context.<ref>PMID:12011435</ref> <ref>PMID:12368292</ref> <ref>PMID:15665000</ref> <ref>PMID:15993959</ref> <ref>PMID:18042454</ref> <ref>PMID:19143053</ref> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| MafA is a proto-oncoprotein and is critical for insulin gene expression in pancreatic beta-cells. Maf proteins belong to the AP1 superfamily of basic region-leucine zipper (bZIP) transcription factors. Residues in the basic helix and an ancillary N-terminal domain, the Extended Homology Region (EHR), endow maf proteins with unique DNA binding properties: binding a 13 bp consensus site consisting of a core AP1 site (TGACTCA) flanked by TGC sequences and binding DNA stably as monomers. To further characterize maf DNA binding, we determined the structure of a MafA-DNA complex. MafA forms base-specific hydrogen bonds with the flanking G(-5)C(-4) and central C(0)/G(0) bases, but not with the core-TGA bases. However, in vitro binding studies utilizing a pulse-chase electrophoretic mobility shift assay protocol revealed that mutating either the core-TGA or flanking-TGC bases dramatically increases the binding off rate. Comparing the known maf structures, we propose that DNA binding specificity results from positioning the basic helix through unique phosphate contacts. The EHR does not contact DNA directly but stabilizes DNA binding by contacting the basic helix. Collectively, these results suggest a novel multistep DNA binding process involving a conformational change from contacting the core-TGA to contacting the flanking-TGC bases.
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| A Novel DNA Binding Mechanism for maf Basic Region-Leucine Zipper Factors Inferred from a MafA-DNA Complex Structure and Binding Specificities.,Lu X, Guanga GP, Wan C, Rose RB Biochemistry. 2012 Nov 20. PMID:23148532<ref>PMID:23148532</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| ==See Also== | | ==See Also== |
| *[[Transcriptional activator|Transcriptional activator]] | | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
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| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Guanga, G]] | | [[Category: Large Structures]] |
| [[Category: Lu, X]] | | [[Category: Guanga G]] |
| [[Category: Rose, R B]] | | [[Category: Lu X]] |
| [[Category: Wan, C]] | | [[Category: Rose RB]] |
| [[Category: Dna binding]]
| | [[Category: Wan C]] |
| [[Category: Leucine zipper]]
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| [[Category: Nucleus]]
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| [[Category: Transcription factor]]
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| [[Category: Transcription-dna complex]]
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