View source for 2nnu


==Crystal Structure of the Papillomavirus DNA Tethering Complex E2:Brd4==
<StructureSection load='2nnu' size='340' side='right'caption='[[2nnu]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nnu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_papillomavirus_type_16 Human papillomavirus type 16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NNU 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]] 1.59&#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=2nnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nnu OCA], [https://pdbe.org/2nnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nnu RCSB], [https://www.ebi.ac.uk/pdbsum/2nnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nnu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VE2_HPV16 VE2_HPV16] Plays an accessory role in initiation of DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex.<ref>PMID:3033289</ref> <ref>PMID:1326651</ref> <ref>PMID:15681049</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/nn/2nnu_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=2nnu ConSurf].
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== Publication Abstract from PubMed ==
Many DNA viruses that are latent in dividing cells are noncovalent passengers on mitotic chromosomes and require specific viral-encoded and cellular factors for this activity. The chromosomal protein Brd4 is implicated in the hitchhiking of bovine papillomavirus-1 (BPV-1), and the viral protein E2 binds to both plasmids and Brd4. Here, we present the X-ray crystal structure of the carboxy-terminal domain of Brd4 in complex with HPV-16 E2, and with this information have developed a Brd4-Tat fusion protein that is efficiently taken up by different transformed cells harboring HPV plasmids. In cells treated with these fusion proteins for only 2 hr and arrested in metaphase, the HPV DNA, either HPV-16 or -31, is displaced from mitotic chromosomes. Mutant Brd4 peptides are deficient in ablating this association. We suggest that such peptides may lead to the development of inhibitors of latency for many, if not all, papillomaviruses.

Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association.,Abbate EA, Voitenleitner C, Botchan MR Mol Cell. 2006 Dec 28;24(6):877-89. PMID:17189190<ref>PMID:17189190</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2nnu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Regulatory protein E2|Regulatory protein E2]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human papillomavirus type 16]]
[[Category: Large Structures]]
[[Category: Abbate EA]]
[[Category: Botchan MR]]
[[Category: Voitenleitner C]]