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PDBsum entry 2fk4
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protein metals links
Metal binding protein, oncoprotein PDB id
2fk4

 

 

 

 

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Contents
Protein chain
67 a.a. *
Metals
_ZN
* Residue conservation analysis
PDB id:
2fk4
Name: Metal binding protein, oncoprotein
Title: Solution structure of thE C-terminal zinc binding domain of the hpv16 e6 oncoprotein
Structure: Protein e6. Chain: a. Fragment: c-terminal domain. Engineered: yes. Mutation: yes
Source: Human papillomavirus type 16. Organism_taxid: 333760. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 10 models
Authors: Y.Nomine,S.Charbonnier
Key ref:
Y.Nominé et al. (2006). Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis. Mol Cell, 21, 665-678. PubMed id: 16507364 DOI: 10.1016/j.molcel.2006.01.024
Date:
04-Jan-06     Release date:   24-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P03126  (VE6_HPV16) -  Protein E6 from Human papillomavirus type 16
Seq:
Struc: 		158 a.a.
67 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1016/j.molcel.2006.01.024 Mol Cell 21:665-678 (2006)
PubMed id: 16507364  
 
 
Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis.
Y.Nominé, M.Masson, S.Charbonnier, K.Zanier, T.Ristriani, F.Deryckère, A.P.Sibler, D.Desplancq, R.A.Atkinson, E.Weiss, G.Orfanoudakis, B.Kieffer, G.Travé.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Solution Structure of E6C 		Figure 4.
Figure 4. Examples of Residue Specialization in HPV Species
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 21, 665-678) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20842623 S.Fournane, S.Charbonnier, A.Chapelle, B.Kieffer, G.Orfanoudakis, G.Travé, M.Masson, and Y.Nominé (2011).
Surface plasmon resonance analysis of the binding of high-risk mucosal HPV E6 oncoproteins to the PDZ1 domain of the tight junction protein MAGI-1.
  J Mol Recognit, 24, 511-523.  
20383192 C.Richard, C.Lanner, S.N.Naryzhny, L.Sherman, H.Lee, P.F.Lambert, and I.Zehbe (2010).
The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer.
  Oncogene, 29, 3435-3445.  
20667709 L.Civit, A.Fragoso, and C.K.O'Sullivan (2010).
Electrochemical biosensor for the multiplexed detection of human papillomavirus genes.
  Biosens Bioelectron, 26, 1684-1687.  
  20862247 L.Fu, K.Van Doorslaer, Z.Chen, T.Ristriani, M.Masson, G.Travé, and R.D.Burk (2010).
Degradation of p53 by human Alphapapillomavirus E6 proteins shows a stronger correlation with phylogeny than oncogenicity.
  PLoS One, 5, 0.  
20155448 Q.Mei, S.Li, P.Liu, L.Xi, S.Wang, Y.Meng, J.Liu, X.Yang, Y.Lu, and H.Wang (2010).
Construction and identification of a yeast two-hybrid bait vector and its effect on the growth of yeast cells and the self-activating function of reporter genes for screening of HPV18 E6-interacting protein.
  J Huazhong Univ Sci Technolog Med Sci, 30, 8.  
19906919 S.S.Tungteakkhun, M.Filippova, N.Fodor, and P.J.Duerksen-Hughes (2010).
The full-length isoform of human papillomavirus 16 E6 and its splice variant E6* bind to different sites on the procaspase 8 death effector domain.
  J Virol, 84, 1453-1463.  
19081593 H.L.Howie, R.A.Katzenellenbogen, and D.A.Galloway (2009).
Papillomavirus E6 proteins.
  Virology, 384, 324-334.  
19553340 K.Van Doorslaer, A.O.Sidi, K.Zanier, V.Rybin, F.Deryckère, A.Rector, R.D.Burk, E.K.Lienau, M.van Ranst, and G.Travé (2009).
Identification of unusual E6 and E7 proteins within avian papillomaviruses: cellular localization, biophysical characterization, and phylogenetic analysis.
  J Virol, 83, 8759-8770.  
19099279 S.Dymalla, M.Scheffner, E.Weber, P.Sehr, C.Lohrey, F.Hoppe-Seyler, and K.Hoppe-Seyler (2009).
A novel peptide motif binding to and blocking the intracellular activity of the human papillomavirus E6 oncoprotein.
  J Mol Med, 87, 321-331.  
19588503 T.F.Schulz (2009).
Cancer and viral infections in immunocompromised individuals.
  Int J Cancer, 125, 1755-1763.  
19015633 T.Ristriani, S.Fournane, G.Orfanoudakis, G.Travé, and M.Masson (2009).
A single-codon mutation converts HPV16 E6 oncoprotein into a potential tumor suppressor, which induces p53-dependent senescence of HPV-positive HeLa cervical cancer cells.
  Oncogene, 28, 762-772.  
19244625 Y.Liu, J.J.Cherry, J.V.Dineen, E.J.Androphy, and J.D.Baleja (2009).
Determinants of stability for the E6 protein of papillomavirus type 16.
  J Mol Biol, 386, 1123-1137.  
18050361 A.P.Sibler, M.Baltzinger, L.Choulier, D.Desplancq, and D.Altschuh (2008).
SPR identification of mild elution conditions for affinity purification of E6 oncoprotein, using a multivariate experimental design.
  J Mol Recognit, 21, 46-54.  
18663566 D.M.Cerqueira, T.Raiol, N.M.Véras, N.von Gal Milanezi, F.A.Amaral, M.de Macedo Brígido, and C.R.Martins (2008).
New variants of human papillomavirus type 18 identified in central Brazil.
  Virus Genes, 37, 282-287.  
18256157 K.M.Bedard, M.P.Underbrink, H.L.Howie, and D.A.Galloway (2008).
The E6 oncoproteins from human betapapillomaviruses differentially activate telomerase through an E6AP-dependent mechanism and prolong the lifespan of primary keratinocytes.
  J Virol, 82, 3894-3902.  
  18538014 L.Mailly, C.Boulade-Ladame, G.Orfanoudakis, and F.Deryckere (2008).
A novel adenovirus vector for easy cloning in the E3 region downstream of the CMV promoter.
  Virol J, 5, 73.  
18752251 M.Simmonds, and A.Storey (2008).
Identification of the regions of the HPV 5 E6 protein involved in Bak degradation and inhibition of apoptosis.
  Int J Cancer, 123, 2260-2266.  
17942561 P.Sekaric, J.J.Cherry, and E.J.Androphy (2008).
Binding of human papillomavirus type 16 E6 to E6AP is not required for activation of hTERT.
  J Virol, 82, 71-76.  
18563332 R.Liu, D.Pu, Y.Liu, Y.Cheng, L.Yin, T.Li, and L.Zhao (2008).
Induction of SiHa cells apoptosis by nanometer realgar suspension and its mechanism.
  J Huazhong Univ Sci Technolog Med Sci, 28, 317-321.  
19007434 S.Beaudenon, and J.M.Huibregtse (2008).
HPV E6, E6AP and cervical cancer.
  BMC Biochem, 9, S4.  
18632871 S.S.Tungteakkhun, M.Filippova, J.W.Neidigh, N.Fodor, and P.J.Duerksen-Hughes (2008).
The interaction between human papillomavirus type 16 and FADD is mediated by a novel E6 binding domain.
  J Virol, 82, 9600-9614.  
18172569 S.S.Tungteakkhun, and P.J.Duerksen-Hughes (2008).
Cellular binding partners of the human papillomavirus E6 protein.
  Arch Virol, 153, 397-408.  
17130828 A.Shai, M.L.Nguyen, J.Wagstaff, Y.H.Jiang, and P.F.Lambert (2007).
HPV16 E6 confers p53-dependent and p53-independent phenotypes in the epidermis of mice deficient for E6AP.
  Oncogene, 26, 3321-3328.  
17287269 C.H.Storrs, and S.J.Silverstein (2007).
PATJ, a tight junction-associated PDZ protein, is a novel degradation target of high-risk human papillomavirus E6 and the alternatively spliced isoform 18 E6.
  J Virol, 81, 4080-4090.  
17023019 N.Brimer, C.Lyons, and S.B.Vande Pol (2007).
Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein.
  Virology, 358, 303-310.  
17224909 S.Camus, S.Menéndez, C.F.Cheok, L.F.Stevenson, S.Laín, and D.P.Lane (2007).
Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6.
  Oncogene, 26, 4059-4070.  
17854024 Y.Asadurian, H.Kurilin, H.Lichtig, A.Jackman, P.Gonen, M.Tommasino, I.Zehbe, and L.Sherman (2007).
Activities of human papillomavirus 16 E6 natural variants in human keratinocytes.
  J Med Virol, 79, 1751-1760.  
17132731 I.Paul, J.Cui, and E.L.Maynard (2006).
Zinc binding to the HCCH motif of HIV-1 virion infectivity factor induces a conformational change that mediates protein-protein interactions.
  Proc Natl Acad Sci U S A, 103, 18475-18480.  
16690141 J.D.Baleja, J.J.Cherry, Z.Liu, H.Gao, M.C.Nicklaus, J.H.Voigt, J.J.Chen, and E.J.Androphy (2006).
Identification of inhibitors to papillomavirus type 16 E6 protein based on three-dimensional structures of interacting proteins.
  Antiviral Res, 72, 49-59.  
17446671 T.Kanda, and I.Kukimoto (2006).
[Human papillomavirus and cervical cancer]
  Uirusu, 56, 219-230.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.

 

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