4fb3
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fb3]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus_polyomavirus_1 Mus musculus polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FB3 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4fb3]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus_polyomavirus_1 Mus musculus polyomavirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FB3 FirstGlance]. <br> | ||
| - | </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=4fb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fb3 OCA], [https://pdbe.org/4fb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fb3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fb3 ProSAT]</span></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]] 3.79Å</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=4fb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fb3 OCA], [https://pdbe.org/4fb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fb3 RCSB], [https://www.ebi.ac.uk/pdbsum/4fb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fb3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/LT_POVBG LT_POVBG] 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.[UniProtKB:P03070] | [https://www.uniprot.org/uniprot/LT_POVBG LT_POVBG] 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.[UniProtKB:P03070] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Polyomaviruses have repeating sequences at their origin of replication that bind the origin-binding domain of virally-encoded large T-antigen. In murine polyomavirus, the central region of the origin contains four copies (P1-P4) of the sequence G(A/G)GGC. These are arranged as a pair of inverted repeats with a two base pair overlap between the repeats at the center. In contrast to SV40, where the repeats are non-overlapping and all four repeats can be simultaneously occupied, the crystal structure of the four central murine polyomavirus sequence repeats in complex with the polyomavirus origin-binding domain reveals that only three of the four repeats (P1,P2, P4) are occupied. Isothermal titration calorimetry confirms that the stoichiometry is the same in solution as in the crystal structure. Consistent with these results, mutation of the third repeat has little effect on DNA replication in vivo. Thus, the apparent two-fold symmetry within the DNA repeats is not carried over to the protein-DNA complex. Flanking sequences such as the A/T rich region are known to be important for DNA replication. When the orientation of the central region was reversed with respect to these flanking regions, the origin was still able to replicate and the P3 sequence (now located at the P2 position with respect to the flanking regions) was again dispensable. This highlights the critical importance of the precise sequence of the region containing the pentamers in replication. | ||
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| - | Polyomavirus Large T-antigen Binds Symmetrical Repeats at the Viral Origin in an Asymmetrical Manner.,Harrison C, Jiang T, Banerjee P, Meinke G, D'Abramo CM, Schaffhausen B, Bohm A J Virol. 2013 Oct 9. PMID:24109229<ref>PMID:24109229</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4fb3" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Large T Antigen|Large T Antigen]] | *[[Large T Antigen|Large T Antigen]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Polyomavirus T-ag binds symmetrical repeats at the viral origin in an asymmetrical manner
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