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4giz

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Revision as of 16:40, 4 August 2016

Crystal structure of full-length human papillomavirus oncoprotein E6 in complex with LXXLL peptide of ubiquitin ligase E6AP at 2.55 A resolution

Structural highlights

4giz is a 4 chain structure with sequence from Hpv16 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	malE, b4034, JW3994 (HUMAN), E6 (HPV16)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [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]

Publication Abstract from PubMed

E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses in vertebrates, including cervical cancer in humans. E6 proteins target many host proteins by specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus E6 proteins bound to LxxLL peptides from the focal adhesion protein paxillin and the ubiquitin ligase E6AP, respectively. In both E6 proteins, two zinc domains and a linker helix form a basic-hydrophobic pocket, which captures helical LxxLL motifs in a way compatible with other interaction modes. Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins.

Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins.,Zanier K, Charbonnier S, Sidi AO, McEwen AG, Ferrario MG, Poussin-Courmontagne P, Cura V, Brimer N, Babah KO, Ansari T, Muller I, Stote RH, Cavarelli J, Vande Pol S, Trave G Science. 2013 Feb 8;339(6120):694-8. doi: 10.1126/science.1229934. PMID:23393263^[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
↑ Zanier K, Charbonnier S, Sidi AO, McEwen AG, Ferrario MG, Poussin-Courmontagne P, Cura V, Brimer N, Babah KO, Ansari T, Muller I, Stote RH, Cavarelli J, Vande Pol S, Trave G. Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science. 2013 Feb 8;339(6120):694-8. doi: 10.1126/science.1229934. PMID:23393263 doi:http://dx.doi.org/10.1126/science.1229934

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4giz"

@@ Line 1: / Line 1: @@
 ==Crystal structure of full-length human papillomavirus oncoprotein E6 in complex with LXXLL peptide of ubiquitin ligase E6AP at 2.55 A resolution==
 <StructureSection load='4giz' size='340' side='right' caption='[[4giz]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4giz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://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=4GIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GIZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4giz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hpv16 Hpv16] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GIZ FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CEY:ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSYL-(1- 4)-ALPHA-D-GLUCOPYRANOSE'>CEY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">malE, b4034, JW3994 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), E6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=333760 Human papillomavirus type 16])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">malE, b4034, JW3994 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), E6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=333760 HPV16])</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=4giz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4giz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4giz RCSB], [http://www.ebi.ac.uk/pdbsum/4giz 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=4giz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4giz OCA], [http://pdbe.org/4giz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4giz RCSB], [http://www.ebi.ac.uk/pdbsum/4giz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4giz ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4giz" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Hpv16]]
 [[Category: Human]]
-[[Category: Human papillomavirus type 16]]
 [[Category: Cavarelli, J]]
 [[Category: Charbonnier, S]]

4giz

From Proteopedia

Revision as of 16:40, 4 August 2016

Crystal structure of full-length human papillomavirus oncoprotein E6 in complex with LXXLL peptide of ubiquitin ligase E6AP at 2.55 A resolution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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