2FK4
Solution structure of the C-terminal zinc binding domain of the HPV16 E6 oncoprotein
Summary for 2FK4
| Entry DOI | 10.2210/pdb2fk4/pdb |
| NMR Information | BMRB: 6407 |
| Descriptor | Protein E6, ZINC ION (2 entities in total) |
| Functional Keywords | zinc binding domain, oncoprotein, metal binding protein |
| Biological source | Human papillomavirus type 16 |
| Cellular location | Host nucleus matrix: P03126 |
| Total number of polymer chains | 1 |
| Total formula weight | 8970.64 |
| Authors | Nomine, Y.,Charbonnier, S. (deposition date: 2006-01-04, release date: 2006-01-24, Last modification date: 2024-05-29) |
| Primary citation | Nomine, Y.,Masson, M.,Charbonnier, S.,Zanier, K.,Ristriani, T.,Deryckere, F.,Sibler, A.P.,Desplancq, D.,Atkinson, R.A.,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, 21:665-678, 2006 Cited by PubMed 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. PubMed: 16507364DOI: 10.1016/j.molcel.2006.01.024 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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