2FK4

Solution structure of the C-terminal zinc binding domain of the HPV16 E6 oncoprotein

2FK4 の概要

• エントリーDOI: 10.2210/pdb2fk4/pdb
• NMR情報: BMRB: 6407
• 分子名称: Protein E6, ZINC ION (2 entities in total)
• 機能のキーワード: zinc binding domain, oncoprotein, metal binding protein
• 由来する生物種: Human papillomavirus type 16
• 細胞内の位置: Host nucleus matrix: P03126
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 8970.64

構造登録者

Nomine, Y.,Charbonnier, S. (登録日: 2006-01-04, 公開日: 2006-01-24, 最終更新日: 2024-05-29)

主引用文献

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

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: 16507364
DOI: 10.1016/j.molcel.2006.01.024

実験手法

SOLUTION NMR