2LJY

Haddock model structure of the N-terminal domain dimer of HPV16 E6

Summary for 2LJY

• Entry DOI: 10.2210/pdb2ljy/pdb
• Related: 2LJZ 2ljx
• NMR Information: BMRB: 17968
• Descriptor: Protein E6, ZINC ION (2 entities in total)
• Functional Keywords: metal binding protein
• Biological source: Human papillomavirus
• Cellular location: Host nucleus matrix: P03126
• Total number of polymer chains: 2
• Total formula weight: 20408.16

Authors

Zanier, K.,Muhamed Sidi, A.,Boulade-Ladame, C.,Rybin, V.,Chappelle, A.,Atkinson, A.,Kieffer, B.,Trave, G. (deposition date: 2011-09-30, release date: 2012-04-04, Last modification date: 2024-05-01)

Primary citation

Zanier, K.,Ould M'hamed Ould Sidi, A.,Boulade-Ladame, C.,Rybin, V.,Chappelle, A.,Atkinson, A.,Kieffer, B.,Trave, G.
Solution Structure Analysis of the HPV16 E6 Oncoprotein Reveals a Self-Association Mechanism Required for E6-Mediated Degradation of p53.
Structure, 20:604-617, 2012

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.

PubMed: 22483108
DOI: 10.1016/j.str.2012.02.001

Experimental method

SOLUTION NMR