View source for 1tbd


==SOLUTION STRUCTURE OF THE ORIGIN DNA BINDING DOMAIN OF SV40 T-ANTIGEN, NMR, MINIMIZED AVERAGE STRUCTURE==
<StructureSection load='1tbd' size='340' side='right'caption='[[1tbd]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tbd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta_polyomavirus_1 Macaca mulatta polyomavirus 1]. The November 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Simian Virus 40''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_11 10.2210/rcsb_pdb/mom_2003_11]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TBD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1tbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tbd OCA], [https://pdbe.org/1tbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tbd RCSB], [https://www.ebi.ac.uk/pdbsum/1tbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tbd ProSAT]</span></td></tr>
</table>
== Function ==
[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 ==
[[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/tb/1tbd_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=1tbd ConSurf].
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== Publication Abstract from PubMed ==
The structure of the domain from simian virus 40 (SV40) large T-antigen that binds to the SV40 origin of DNA replication (T-ag-OBD131-260) has been determined by nuclear magnetic resonance spectroscopy. The overall fold, consisting of a central five-stranded antiparallel beta-sheet flanked by two alpha-helices on one side and one alpha-helix and one 3(10)-helix on the other, is a new one. Previous mutational analyses have identified two elements, termed A (approximately 152-155) and B2 (203-207), as essential for origin-specific recognition. These elements form two closely juxtaposed loops that define a continuous surface on the protein. The addition of a duplex oligonucleotide containing the origin recognition pentanucleotide GAGGC induces chemical shift changes and slows amide proton exchange in resonances from this region, indicating that this surface directly contacts the DNA.

Solution structure of the origin DNA-binding domain of SV40 T-antigen.,Luo X, Sanford DG, Bullock PA, Bachovchin WW Nat Struct Biol. 1996 Dec;3(12):1034-9. PMID:8946857<ref>PMID:8946857</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Large T Antigen|Large T Antigen]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Macaca mulatta polyomavirus 1]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Simian Virus 40]]
[[Category: Bachovchin WW]]
[[Category: Bullock PA]]
[[Category: Luo X]]
[[Category: Sanford DG]]