2pi0

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[[Image:2pi0.png|left|200px]]
 
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{{STRUCTURE_2pi0| PDB=2pi0 | SCENE= }}
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==Crystal Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-B enhancer==
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<StructureSection load='2pi0' size='340' side='right'caption='[[2pi0]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pi0]] 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=2PI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PI0 FirstGlance]. <br>
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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]] 2.31&#8491;</td></tr>
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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=2pi0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pi0 OCA], [https://pdbe.org/2pi0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pi0 RCSB], [https://www.ebi.ac.uk/pdbsum/2pi0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pi0 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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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/pi/2pi0_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=2pi0 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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Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the assembly of the mammalian interferon-beta (IFN-beta) enhanceosome. We present here the structure of IRF-3 DNA binding domain in complex with the complete PRDIII-I regulatory element of the human IFN-beta enhancer. We show that four IRF-3 molecules bind in tandem to, variably spaced, consensus and nonconsensus IRF sites on the composite element. The ability of IRF-3 to bind these variable sites derives in part from two nonconserved arginines (Arg78 and Arg86) that partake in alternate protein-DNA contacts. We also show that the protein-DNA contacts are highly overlapped and that all four IRF sites are required for gene activation in vivo. In addition, we show that changing the nonconsensus IRF sites to consensus sites creates a more efficient enhancer in vivo. Together, the structure and accompanying biological data provide insights into the assembly of the IFN-beta enhanceosome in mammals.
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===Crystal Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-B enhancer===
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Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer.,Escalante CR, Nistal-Villan E, Shen L, Garcia-Sastre A, Aggarwal AK Mol Cell. 2007 Jun 8;26(5):703-16. PMID:17560375<ref>PMID:17560375</ref>
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{{ABSTRACT_PUBMED_17560375}}
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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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==About this Structure==
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<div class="pdbe-citations 2pi0" style="background-color:#fffaf0;"></div>
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[[2pi0]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2010 RCSB PDB [http://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 [http://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=2PI0 OCA].
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==See Also==
==See Also==
*[[Interferon regulatory factor|Interferon regulatory factor]]
*[[Interferon regulatory factor|Interferon regulatory factor]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017560375</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Enhanceosome]]
[[Category: Enhanceosome]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Aggarwal, A K.]]
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[[Category: Aggarwal AK]]
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[[Category: Escalante, C R.]]
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[[Category: Escalante CR]]
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[[Category: Garcia-Sastre, A.]]
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[[Category: Garcia-Sastre A]]
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[[Category: Leyi, S.]]
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[[Category: Leyi S]]
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[[Category: Nistal-Villan, E.]]
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[[Category: Nistal-Villan E]]
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[[Category: Interferon]]
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[[Category: Protein-dna complex]]
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[[Category: Transcription]]
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[[Category: Transcription activator-dna complex]]
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Current revision

Crystal Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-B enhancer

PDB ID 2pi0

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