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[[Image:2jeu.jpg|left|200px]]
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{{STRUCTURE_2jeu|  PDB=2jeu  |  SCENE=  }}
'''TRANSCRIPTION ACTIVATOR STRUCTURE REVEALS REDOX CONTROL OF A REPLICATION INITIATION REACTION'''


==Transcription activator structure reveals redox control of a replication initiation reaction==
<StructureSection load='2jeu' size='340' side='right'caption='[[2jeu]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jeu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Deltapapillomavirus_4 Deltapapillomavirus 4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JEU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JEU 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]] 2.8&#8491;</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=2jeu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jeu OCA], [https://pdbe.org/2jeu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jeu RCSB], [https://www.ebi.ac.uk/pdbsum/2jeu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jeu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VE2_BPV1 VE2_BPV1] E2 regulates viral transcription and DNA replication. Binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. Can either activate or repress transcription depending on E2RE's position with regards to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E1-E2 complex binds to the origin of DNA replication.
== 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/je/2jeu_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=2jeu ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. Proteins regulated through redox-sensitive cysteines have been characterized but specific 'sulphydryl switches' in replication proteins remain to be identified. In bovine papillomavirus type-1, DNA replication begins when the viral transcription factor E2 recruits the viral initiator protein E1 to the origin of DNA replication (ori). Here we show that a novel dimerization interface in the E2 transcription activation domain is stabilized by a disulphide bond. Oxidative cross-linking via Cys57 sequesters the interaction surface between E1 and E2, preventing pre-initiation and replication initiation complex formation. Our data demonstrate that as well as a mechanism for regulating DNA binding, redox reactions can control replication by modulating the tertiary structure of critical protein factors using a specific redox sensor.


==Overview==
Transcription activator structure reveals redox control of a replication initiation reaction.,Sanders CM, Sizov D, Seavers PR, Ortiz-Lombardia M, Antson AA Nucleic Acids Res. 2007;35(10):3504-15. Epub 2007 May 3. PMID:17478495<ref>PMID:17478495</ref>
Redox changes are one of the factors that influence cell-cycle progression and that control the processes of cellular proliferation, differentiation, senescence and apoptosis. Proteins regulated through redox-sensitive cysteines have been characterized but specific 'sulphydryl switches' in replication proteins remain to be identified. In bovine papillomavirus type-1, DNA replication begins when the viral transcription factor E2 recruits the viral initiator protein E1 to the origin of DNA replication (ori). Here we show that a novel dimerization interface in the E2 transcription activation domain is stabilized by a disulphide bond. Oxidative cross-linking via Cys57 sequesters the interaction surface between E1 and E2, preventing pre-initiation and replication initiation complex formation. Our data demonstrate that as well as a mechanism for regulating DNA binding, redox reactions can control replication by modulating the tertiary structure of critical protein factors using a specific redox sensor.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2JEU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bovine_papillomavirus_type_1 Bovine papillomavirus type 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JEU OCA].
</div>
<div class="pdbe-citations 2jeu" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Transcription activator structure reveals redox control of a replication initiation reaction., Sanders CM, Sizov D, Seavers PR, Ortiz-Lombardia M, Antson AA, Nucleic Acids Res. 2007;35(10):3504-15. Epub 2007 May 3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17478495 17478495]
*[[Regulatory protein E2|Regulatory protein E2]]
[[Category: Bovine papillomavirus type 1]]
== References ==
[[Category: Single protein]]
<references/>
[[Category: Antson, A A.]]
__TOC__
[[Category: Ortiz-Lombardia, M.]]
</StructureSection>
[[Category: Sanders, C M.]]
[[Category: Deltapapillomavirus 4]]
[[Category: Seavers, P R.]]
[[Category: Large Structures]]
[[Category: Sizov, D.]]
[[Category: Antson AA]]
[[Category: Activator]]
[[Category: Ortiz-Lombardia M]]
[[Category: Bovine papillomavirus]]
[[Category: Sanders CM]]
[[Category: Dna replication]]
[[Category: Seavers PR]]
[[Category: Dna-binding]]
[[Category: Sizov D]]
[[Category: E1]]
[[Category: E2]]
[[Category: Early protein]]
[[Category: Nuclear protein]]
[[Category: Oxidation]]
[[Category: Phosphorylation]]
[[Category: Redox control]]
[[Category: Replication initiation]]
[[Category: Repressor]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Viral transcription factor]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:48:10 2008''