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==CRYSTAL STRUCTURE OF THE HPV-18 E2 DNA-BINDING DOMAIN==
==CRYSTAL STRUCTURE OF THE HPV-18 E2 DNA-BINDING DOMAIN==
<StructureSection load='1f9f' size='340' side='right' caption='[[1f9f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='1f9f' size='340' side='right'caption='[[1f9f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1f9f]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_papillomavirus_type_18 Human papillomavirus type 18]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F9F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1F9F FirstGlance]. <br>
<table><tr><td colspan='2'>[[1f9f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_type_18 Human papillomavirus type 18]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F9F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.9&#8491;</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=1f9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f9f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1f9f RCSB], [http://www.ebi.ac.uk/pdbsum/1f9f PDBsum]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1f9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f9f OCA], [https://pdbe.org/1f9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f9f RCSB], [https://www.ebi.ac.uk/pdbsum/1f9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f9f ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VE2_HPV18 VE2_HPV18] E2 regulates viral transcription and DNA replication. It binds to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory region. It 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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/1f9f_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f9/1f9f_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=1f9f ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The papillomavirus E2 proteins regulate the transcription of all papillomavirus genes and are necessary for viral DNA replication. Disruption of the E2 gene is commonly associated with malignancy in cervical carcinoma, indicating that E2 has a role in regulating tumor progression. Although the E2 proteins from all characterized papillomaviruses bind specifically to the same 12-base pair DNA sequence, the cancer-associated human papillomavirus E2 proteins display a unique ability to detect DNA flexibility and intrinsic curvature. To understand the structural basis for this phenomenon, we have determined the crystal structures of the human papillomavirus-18 E2 DNA-binding domain and its complexes with high and low affinity binding sites. The E2 protein is a dimeric beta-barrel and the E2-DNA interaction is accompanied by a large deformation of the DNA as it conforms to the E2 surface. DNA conformation and E2-DNA contacts are similar in both high and low affinity complexes. The differences in affinity correlate with the flexibility of the DNA sequence. Preferences of E2 proteins from different papillomavirus strains for flexible or prevent DNA targets correlate with the distribution of positive charge on their DNA interaction surfaces, suggesting a role for electrostatic forces in the recognition of DNA deformability.
The structural basis of DNA target discrimination by papillomavirus E2 proteins.,Kim SS, Tam JK, Wang AF, Hegde RS J Biol Chem. 2000 Oct 6;275(40):31245-54. PMID:10906136<ref>PMID:10906136</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Regulatory protein E2|Regulatory protein E2]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human papillomavirus type 18]]
[[Category: Human papillomavirus type 18]]
[[Category: Hegde, R]]
[[Category: Large Structures]]
[[Category: Kim, S S]]
[[Category: Hegde R]]
[[Category: Tam, J]]
[[Category: Kim SS]]
[[Category: Wang, A F]]
[[Category: Tam J]]
[[Category: Activator]]
[[Category: Wang AF]]
[[Category: Dimeric beta barrel]]
[[Category: Dna-binding]]
[[Category: Trans-acting factor]]
[[Category: Transcription]]

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