2fuf

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[[Image:2fuf.png|left|200px]]
 
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{{STRUCTURE_2fuf| PDB=2fuf | SCENE= }}
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==Crystal structure of the SV40 large T antigen origin-binding domain==
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<StructureSection load='2fuf' size='340' side='right'caption='[[2fuf]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2fuf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta_polyomavirus_1 Macaca mulatta polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FUF 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]] 1.45&#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=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=2fuf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fuf OCA], [https://pdbe.org/2fuf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fuf RCSB], [https://www.ebi.ac.uk/pdbsum/2fuf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fuf ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/LT_SV40 LT_SV40] Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription. May inactivate the growth-suppressing properties of the E3 ubiquitin ligase CUL7.<ref>PMID:8647434</ref> <ref>PMID:9632777</ref> <ref>PMID:9488456</ref> <ref>PMID:15680424</ref> <ref>PMID:15611062</ref> <ref>PMID:17341466</ref> <ref>PMID:18922873</ref> Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain.<ref>PMID:8647434</ref> <ref>PMID:9632777</ref> <ref>PMID:9488456</ref> <ref>PMID:15680424</ref> <ref>PMID:15611062</ref> <ref>PMID:17341466</ref> <ref>PMID:18922873</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/fu/2fuf_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2fuf 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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The origins of replication of DNA tumor viruses have a highly conserved feature, namely, multiple binding sites for their respective initiator proteins arranged as inverted repeats. In the 1.45-angstroms crystal structure of the simian virus 40 large T-antigen (T-ag) origin-binding domain (obd) reported herein, T-ag obd monomers form a left-handed spiral with an inner channel of 30 angstroms having six monomers per turn. The inner surface of the spiral is positively charged and includes residues known to bind DNA. Residues implicated in hexamerization of full-length T-ag are located at the interface between adjacent T-ag obd monomers. These data provide a high-resolution model of the hexamer of origin-binding domains observed in electron microscopy studies and allow the obd's to be oriented relative to the hexamer of T-ag helicase domains to which they are connected.
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===Crystal structure of the SV40 large T antigen origin-binding domain===
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Crystal structure of the simian virus 40 large T-antigen origin-binding domain.,Meinke G, Bullock PA, Bohm A J Virol. 2006 May;80(9):4304-12. PMID:16611889<ref>PMID:16611889</ref>
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{{ABSTRACT_PUBMED_16611889}}
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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 2fuf" style="background-color:#fffaf0;"></div>
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[[2fuf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Simian_virus_40 Simian virus 40]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FUF OCA].
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==See Also==
==See Also==
*[[Large T Antigen|Large T Antigen]]
*[[Large T Antigen|Large T Antigen]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:016611889</ref><ref group="xtra">PMID:017253903</ref><references group="xtra"/>
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__TOC__
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[[Category: Simian virus 40]]
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</StructureSection>
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[[Category: Bohm, A.]]
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[[Category: Large Structures]]
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[[Category: Bullock, P A.]]
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[[Category: Macaca mulatta polyomavirus 1]]
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[[Category: Meinke, G.]]
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[[Category: Bohm A]]
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[[Category: Dna binding protein]]
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[[Category: Bullock PA]]
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[[Category: Dna replication]]
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[[Category: Meinke G]]
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[[Category: Replication origin binding domain]]
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Current revision

Crystal structure of the SV40 large T antigen origin-binding domain

PDB ID 2fuf

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Proteopedia Page Contributors and Editors (what is this?)

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