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3qk2

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Revision as of 16:00, 4 August 2016

Structure-Based Analysis of the Interaction between the Simian Virus 40 T-Antigen Origin Binding Domain and Single-Stranded DNA

Structural highlights

3qk2 is a 1 chain structure with sequence from Polyomavirus maccacae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	2fuf, 2ntc, 2itl, 2if9
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]

Publication Abstract from PubMed

The origin-binding domain (OBD) of simian virus 40 (SV40) large T-antigen (T-Ag) is essential for many of T-Ag's interactions with DNA. Nevertheless, many important issues related to DNA binding, for example, how single-stranded DNA (ssDNA) transits along the T-Ag OBD, have yet to be established. Therefore, X-ray crystallography was used to determine the costructure of the T-Ag OBD bound to DNA substrates such as the single-stranded region of a forked oligonucleotide. A second structure of the T-Ag OBD crystallized in the presence of poly(dT)(12) is also reported. To test the conclusions derived from these structures, residues identified as being involved in binding to ssDNA by crystallography or by an earlier nuclear magnetic resonance study were mutated, and their binding to DNA was characterized via fluorescence anisotropy. In addition, these mutations were introduced into full-length T-Ag, and these mutants were tested for their ability to support replication. When considered in terms of additional homology-based sequence alignments, our studies refine our understanding of how the T-Ag OBDs encoded by the polyomavirus family interact with ssDNA, a critical step during the initiation of DNA replication.

Structure-based analysis of the interaction between the simian virus 40 T-antigen origin binding domain and single-stranded DNA.,Meinke G, Phelan PJ, Fradet-Turcotte A, Bohm A, Archambault J, Bullock PA J Virol. 2011 Jan;85(2):818-27. Epub 2010 Oct 27. PMID:20980496^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Damania B, Alwine JC. TAF-like function of SV40 large T antigen. Genes Dev. 1996 Jun 1;10(11):1369-81. PMID:8647434
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Meinke G, Phelan PJ, Fradet-Turcotte A, Bohm A, Archambault J, Bullock PA. Structure-based analysis of the interaction between the simian virus 40 T-antigen origin binding domain and single-stranded DNA. J Virol. 2011 Jan;85(2):818-27. Epub 2010 Oct 27. PMID:20980496 doi:10.1128/JVI.01738-10

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qk2"

@@ Line 1: / Line 1: @@
 ==Structure-Based Analysis of the Interaction between the Simian Virus 40 T-Antigen Origin Binding Domain and Single-Stranded DNA==
 <StructureSection load='3qk2' size='340' side='right' caption='[[3qk2]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3qk2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Simian_virus_40 Simian virus 40]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QK2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3qk2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Polyomavirus_maccacae Polyomavirus maccacae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QK2 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fuf|2fuf]], [[2ntc|2ntc]], [[2itl|2itl]], [[2if9|2if9]]</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=3qk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qk2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qk2 RCSB], [http://www.ebi.ac.uk/pdbsum/3qk2 PDBsum]</span></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=3qk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qk2 OCA], [http://pdbe.org/3qk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qk2 RCSB], [http://www.ebi.ac.uk/pdbsum/3qk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qk2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3qk2" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Simian virus 40]]
+[[Category: Polyomavirus maccacae]]
 [[Category: Bohm, A]]
 [[Category: Bullock, P A]]

3qk2

From Proteopedia

Revision as of 16:00, 4 August 2016

Structure-Based Analysis of the Interaction between the Simian Virus 40 T-Antigen Origin Binding Domain and Single-Stranded DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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