4e2i: Difference between revisions

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'''Unreleased structure'''


The entry 4e2i is ON HOLD
==The Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-Primase==
<StructureSection load='4e2i' size='340' side='right'caption='[[4e2i]], [[Resolution|resolution]] 5.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4e2i]] is a 23 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [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=4E2I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E2I FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[https://proteopedia.org/fgij/fg.htm?mol=4e2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2i OCA], [https://pdbe.org/4e2i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e2i RCSB], [https://www.ebi.ac.uk/pdbsum/4e2i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2i 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>


Authors: Zhou, B., Arnett, D.R., Yu, X., Brewster, A., Sowd, G.A., Xie, C.L., Vila, S., Gai, D., Fanning, E., Chen, X.S.
==See Also==
 
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
Description: The Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-Primase
*[[Large T Antigen|Large T Antigen]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Macaca mulatta polyomavirus 1]]
[[Category: Arnett DR]]
[[Category: Brewster A]]
[[Category: Chen XS]]
[[Category: Fanning E]]
[[Category: Gai D]]
[[Category: Sowd GA]]
[[Category: Vila S]]
[[Category: Xie CL]]
[[Category: Yu X]]
[[Category: Zhou B]]

Latest revision as of 14:01, 1 March 2024

The Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-PrimaseThe Complex Structure of the SV40 Helicase Large T Antigen and p68 Subunit of DNA Polymerase Alpha-Primase

Structural highlights

4e2i is a 23 chain structure with sequence from Homo sapiens and Macaca mulatta polyomavirus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 5Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4] [5] [6] [7] Isoform 17kT antigen targets host RBL2 for degradation and promotes cell proliferation. Transactivates host cyclin A promoter through its J domain.[8] [9] [10] [11] [12] [13] [14]

See Also

References

  1. ↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
  2. ↑ Damania B, Lieberman P, Alwine JC. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Mol Cell Biol. 1998 Jul;18(7):3926-35. PMID:9632777
  3. ↑ Zalvide J, Stubdal H, DeCaprio JA. The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins. Mol Cell Biol. 1998 Mar;18(3):1408-15. PMID:9488456
  4. ↑ Skoczylas C, Henglein B, Rundell K. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site. Virology. 2005 Feb 20;332(2):596-601. PMID:15680424 doi:10.1016/j.virol.2004.12.017
  5. ↑ Welcker M, Clurman BE. The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4. J Biol Chem. 2005 Mar 4;280(9):7654-8. Epub 2004 Dec 20. PMID:15611062 doi:10.1074/jbc.M413377200
  6. ↑ Valls E, Blanco-Garcia N, Aquizu N, Piedra D, Estaras C, de la Cruz X, Martinez-Balbas MA. Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. Nucleic Acids Res. 2007;35(6):1958-68. Epub 2007 Mar 6. PMID:17341466 doi:gkl1113
  7. ↑ Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol. 2009 Jan;83(1):117-27. doi: 10.1128/JVI.01515-08. Epub 2008 Oct 15. PMID:18922873 doi:10.1128/JVI.01515-08
  8. ↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
  9. ↑ Damania B, Lieberman P, Alwine JC. Simian virus 40 large T antigen stabilizes the TATA-binding protein-TFIIA complex on the TATA element. Mol Cell Biol. 1998 Jul;18(7):3926-35. PMID:9632777
  10. ↑ Zalvide J, Stubdal H, DeCaprio JA. The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins. Mol Cell Biol. 1998 Mar;18(3):1408-15. PMID:9488456
  11. ↑ Skoczylas C, Henglein B, Rundell K. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site. Virology. 2005 Feb 20;332(2):596-601. PMID:15680424 doi:10.1016/j.virol.2004.12.017
  12. ↑ Welcker M, Clurman BE. The SV40 large T antigen contains a decoy phosphodegron that mediates its interactions with Fbw7/hCdc4. J Biol Chem. 2005 Mar 4;280(9):7654-8. Epub 2004 Dec 20. PMID:15611062 doi:10.1074/jbc.M413377200
  13. ↑ Valls E, Blanco-Garcia N, Aquizu N, Piedra D, Estaras C, de la Cruz X, Martinez-Balbas MA. Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. Nucleic Acids Res. 2007;35(6):1958-68. Epub 2007 Mar 6. PMID:17341466 doi:gkl1113
  14. ↑ Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol. 2009 Jan;83(1):117-27. doi: 10.1128/JVI.01515-08. Epub 2008 Oct 15. PMID:18922873 doi:10.1128/JVI.01515-08

4e2i, resolution 5.00Å

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