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<StructureSection load='1svm' size='340' side='right'caption='[[1svm]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
<StructureSection load='1svm' size='340' side='right'caption='[[1svm]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1svm]] is a 6 chain structure. The August 2006 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''AAA+ Proteases''  by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2006_8 10.2210/rcsb_pdb/mom_2006_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SVM FirstGlance]. <br>
<table><tr><td colspan='2'>[[1svm]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta_polyomavirus_1 Macaca mulatta polyomavirus 1]. The August 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''AAA+ Proteases''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_8 10.2210/rcsb_pdb/mom_2006_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SVM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.94&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1svl|1svl]], [[1svo|1svo]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1svm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1svm OCA], [http://pdbe.org/1svm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1svm RCSB], [http://www.ebi.ac.uk/pdbsum/1svm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1svm ProSAT]</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=1svm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1svm OCA], [https://pdbe.org/1svm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1svm RCSB], [https://www.ebi.ac.uk/pdbsum/1svm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1svm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1svm ConSurf].
</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=1svm ConSurf].
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<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The large tumor antigen (LTag) of simian virus 40, an AAA(+) protein, is a hexameric helicase essential for viral DNA replication in eukaryotic cells. LTag functions as an efficient molecular machine powered by ATP binding and hydrolysis for origin DNA melting and replication fork unwinding. To understand how ATP binding and hydrolysis are coupled to conformational changes, we have determined high-resolution structures ( approximately 1.9 A) of LTag hexamers in distinct nucleotide binding states. The structural differences of LTag in various nucleotide states detail the molecular mechanisms of conformational changes triggered by ATP binding/hydrolysis and reveal a potential mechanism of concerted nucleotide binding and hydrolysis. During these conformational changes, the angles and orientations between domains of a monomer alter, creating an "iris"-like motion in the hexamer. Additionally, six unique beta hairpins on the channel surface move longitudinally along the central channel, possibly serving as a motor for pulling DNA into the LTag double hexamer for unwinding.
Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen.,Gai D, Zhao R, Li D, Finkielstein CV, Chen XS Cell. 2004 Oct 1;119(1):47-60. PMID:15454080<ref>PMID:15454080</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1svm" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Journal:JSB:1|Journal:JSB:1]]
*[[Large T Antigen|Large T Antigen]]
*[[Large T Antigen|Large T Antigen]]
== References ==
== References ==
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[[Category: AAA+ Proteases]]
[[Category: AAA+ Proteases]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Macaca mulatta polyomavirus 1]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Chen, X S]]
[[Category: Chen XS]]
[[Category: Finkielstein, C V]]
[[Category: Finkielstein CV]]
[[Category: Gai, D]]
[[Category: Gai D]]
[[Category: Zhao, R]]
[[Category: Zhao R]]
[[Category: Aaa+ fold]]
[[Category: Viral protein]]

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