1t2k
From Proteopedia
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| - | [[Image:1t2k.png|left|200px]] | ||
| - | + | ==Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA== | |
| + | <StructureSection load='1t2k' size='340' side='right'caption='[[1t2k]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1t2k]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Enhanceosome'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_2 10.2210/rcsb_pdb/mom_2010_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T2K 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]] 3Å</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=1t2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t2k OCA], [https://pdbe.org/1t2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t2k RCSB], [https://www.ebi.ac.uk/pdbsum/1t2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t2k ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IRF3_HUMAN IRF3_HUMAN] Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages. | ||
| + | == 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/t2/1t2k_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=1t2k ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN-beta gene. The 3.0 A crystal structure of the DNA-binding domains of ATF-2/c-Jun and two IRF-3 molecules in a complex with 31 base pairs (bp) of the PRDIV-PRDIII region of the IFN-beta enhancer shows that association of the four proteins with DNA creates a continuous surface for the recognition of 24 bp. The structure, together with in vitro binding studies and protein mutagenesis, shows that protein-protein interactions are not critical for cooperative binding. Instead, cooperativity arises mainly through nucleotide sequence-dependent structural changes in the DNA that allow formation of complementary DNA conformations. Because the binding sites overlap on the enhancer, the unit of recognition is the entire nucleotide sequence, not the individual subsites. | ||
| - | + | Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer.,Panne D, Maniatis T, Harrison SC EMBO J. 2004 Nov 10;23(22):4384-93. Epub 2004 Oct 28. PMID:15510218<ref>PMID:15510218</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1t2k" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Interferon regulatory factor|Interferon regulatory factor]] | *[[Interferon regulatory factor|Interferon regulatory factor]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Enhanceosome]] | [[Category: Enhanceosome]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: RCSB PDB Molecule of the Month]] | [[Category: RCSB PDB Molecule of the Month]] | ||
| - | [[Category: Harrison | + | [[Category: Harrison SC]] |
| - | [[Category: Maniatis | + | [[Category: Maniatis T]] |
| - | [[Category: Panne | + | [[Category: Panne D]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Structure Of The DNA Binding Domains Of IRF3, ATF-2 and Jun Bound To DNA
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