View source for 2ljz


==Structure of the C-terminal domain of HPV16 E6 oncoprotein==
<StructureSection load='2ljz' size='340' side='right'caption='[[2ljz]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ljz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_type_16 Human papillomavirus type 16]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LJZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LJZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2ljz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ljz OCA], [https://pdbe.org/2ljz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ljz RCSB], [https://www.ebi.ac.uk/pdbsum/2ljz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ljz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VE6_HPV16 VE6_HPV16] Plays a major role in the induction and maintenance of cellular transformation. Acts mainly as an oncoprotein by stimulating the destruction of many host cell key regulatory proteins. E6 associates with host E6-AP ubiquitin-protein ligase, and inactivates tumor suppressors TP53 and TP73 by targeting them to the 26S proteasome for degradation. In turn, DNA damage and chromosomal instabilities increase and lead to cell proliferation and cancer development. The complex E6/E6P targets several other substrates to degradation via the proteasome including host NFX1-91, a repressor of human telomerase reverse transcriptase (hTERT). The resulting increased expression of hTERT prevents the shortening of telomere length leading to cell immortalization. Other cellular targets including Bak, Fas-associated death domain-containing protein (FADD) and procaspase 8, are degraded by E6/E6AP causing inhibition of apoptosis. E6 also inhibits immune response by interacting with host IRF3 and TYK2. These interactions prevent IRF3 transcriptional activities and inhibit TYK2-mediated JAK-STAT activation by interferon alpha resulting in inhibition of the interferon signaling pathway.<ref>PMID:8598912</ref> <ref>PMID:9649509</ref> <ref>PMID:10523853</ref> 
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== Publication Abstract from PubMed ==
The viral oncoprotein E6 is an essential factor for cervical cancers induced by "high-risk" mucosal HPV. Among other oncogenic activities, E6 recruits the ubiquitin ligase E6AP to promote the ubiquitination and subsequent proteasomal degradation of p53. E6 is prone to self-association, which long precluded its structural analysis. Here we found that E6 specifically dimerizes through its N-terminal domain and that disruption of the dimer interface strongly increases E6 solubility. This allowed us to raise structural data covering the entire HPV16 E6 protein, including the high-resolution NMR structures of the two zinc-binding domains of E6 and a robust data-driven model structure of the N-terminal domain homodimer. Interestingly, homodimer interface mutations that disrupt E6 self-association also inactivate E6-mediated p53 degradation. These data suggest that E6 needs to self-associate via its N-terminal domain to promote the polyubiquitination of p53 by E6AP.

Solution Structure Analysis of the HPV16 E6 Oncoprotein Reveals a Self-Association Mechanism Required for E6-Mediated Degradation of p53.,Zanier K, Ould M'hamed Ould Sidi A, Boulade-Ladame C, Rybin V, Chappelle A, Atkinson A, Kieffer B, Trave G Structure. 2012 Apr 4;20(4):604-17. Epub 2012 Apr 3. PMID:22483108<ref>PMID:22483108</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 2ljz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human papillomavirus type 16]]
[[Category: Large Structures]]
[[Category: Atkinson A]]
[[Category: Boulade-Ladame C]]
[[Category: Chappelle A]]
[[Category: Kieffer B]]
[[Category: Muhamed Sidi A]]
[[Category: Rybin V]]
[[Category: Trave G]]
[[Category: Zanier K]]