2LJZ

Structure of the C-terminal domain of HPV16 E6 oncoprotein


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

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.

(2012) Structure 20: 604-617

  • DOI: https://doi.org/10.1016/j.str.2012.02.001
  • Primary Citation of Related Structures:  
    2LJX, 2LJY, 2LJZ

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg (IREBS), Boulevard Sébastien Brant, BP 10413, 67412 Illkirch, France. zanier@unistra.fr


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein E675Human papillomavirus 16Mutation(s): 4 
Gene Names: E6
UniProt
Find proteins for P03126 (Human papillomavirus type 16)
Explore P03126 
Go to UniProtKB:  P03126
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03126
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-04
    Type: Initial release
  • Version 1.1: 2012-04-25
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Derived calculations, Other
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references