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| ==Origin binding domain of the SV40 large T antigen (residues 131-259). P212121 crystal form== | | ==Origin binding domain of the SV40 large T antigen (residues 131-259). P212121 crystal form== |
| <StructureSection load='2itj' size='340' side='right' caption='[[2itj]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2itj' size='340' side='right'caption='[[2itj]], [[Resolution|resolution]] 2.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[2itj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITJ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2itj]] is a 2 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=2ITJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITJ FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ipr|2ipr]], [[2itl|2itl]], [[2nl8|2nl8]]</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]] 2.5Å</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=2itj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itj OCA], [http://pdbe.org/2itj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itj RCSB], [http://www.ebi.ac.uk/pdbsum/2itj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2itj 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=2itj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itj OCA], [https://pdbe.org/2itj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2itj RCSB], [https://www.ebi.ac.uk/pdbsum/2itj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2itj 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/Q98ZP7_SV40 Q98ZP7_SV40] |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bochkarev, A]] | | [[Category: Large Structures]] |
| [[Category: Bochkareva, E]] | | [[Category: Macaca mulatta polyomavirus 1]] |
| [[Category: Martynowski, D]] | | [[Category: Bochkarev A]] |
| [[Category: Dna binding protein]] | | [[Category: Bochkareva E]] |
| | [[Category: Martynowski D]] |