2fk4

From Proteopedia

(Difference between revisions)

Revision as of 07:44, 11 September 2015

Solution structure of the C-terminal zinc binding domain of the HPV16 E6 oncoprotein

Structural highlights

2fk4 is a 1 chain structure with sequence from Hpv16. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Oncoprotein E6 is essential for oncogenesis induced by human papillomaviruses (HPVs). The solution structure of HPV16-E6 C-terminal domain reveals a zinc binding fold. A model of full-length E6 is proposed and analyzed in the context of HPV evolution. E6 appears as a chameleon protein combining a conserved structural scaffold with highly variable surfaces participating in generic or specialized HPV functions. We investigated surface residues involved in two specialized activities of high-risk genital HPV E6: p53 tumor suppressor degradation and nucleic acid binding. Screening of E6 surface mutants identified an in vivo p53 degradation-defective mutant that fails to recruit p53 to ubiquitin ligase E6AP and restores high p53 levels in cervical carcinoma cells by competing with endogeneous E6. We also mapped the nucleic acid binding surface of E6, the positive potential of which correlates with genital oncogenicity. E6 structure-function analysis provides new clues for understanding and counteracting the complex pathways of HPV-mediated pathogenesis.

Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis.,Nomine Y, Masson M, Charbonnier S, Zanier K, Ristriani T, Deryckere F, Sibler AP, Desplancq D, Atkinson RA, Weiss E, Orfanoudakis G, Kieffer B, Trave G Mol Cell. 2006 Mar 3;21(5):665-78. PMID:16507364^[4]

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

References

↑ Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature. 1996 Mar 7;380(6569):79-82. PMID:8598912 doi:http://dx.doi.org/10.1038/380079a0
↑ Ronco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998 Jul 1;12(13):2061-72. PMID:9649509
↑ Li S, Labrecque S, Gauzzi MC, Cuddihy AR, Wong AH, Pellegrini S, Matlashewski GJ, Koromilas AE. The human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alpha. Oncogene. 1999 Oct 14;18(42):5727-37. PMID:10523853 doi:http://dx.doi.org/10.1038/sj.onc.1202960
↑ Nomine Y, Masson M, Charbonnier S, Zanier K, Ristriani T, Deryckere F, Sibler AP, Desplancq D, Atkinson RA, Weiss E, Orfanoudakis G, Kieffer B, Trave G. Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis. Mol Cell. 2006 Mar 3;21(5):665-78. PMID:16507364 doi:10.1016/j.molcel.2006.01.024

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2fk4"

@@ Line 2: / Line 2: @@
 <StructureSection load='2fk4' size='340' side='right' caption='[[2fk4]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2fk4]] is a 1 chain structure with sequence from [http://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=2FK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FK4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2fk4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hpv16 Hpv16]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FK4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fk4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fk4 RCSB], [http://www.ebi.ac.uk/pdbsum/2fk4 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=2fk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fk4 OCA], [http://pdbe.org/2fk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fk4 RCSB], [http://www.ebi.ac.uk/pdbsum/2fk4 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 26: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2fk4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human papillomavirus type 16]]
+[[Category: Hpv16]]
 [[Category: Charbonnier, S]]
 [[Category: Nomine, Y]]

2fk4

From Proteopedia

Revision as of 07:44, 11 September 2015

Solution structure of the C-terminal zinc binding domain of the HPV16 E6 oncoprotein

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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