2fk4

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2fk4

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

Overview

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.

About this Structure

2FK4 is a Single protein structure of sequence from Human papillomavirus type 13 with ZN as ligand. Full crystallographic information is available from OCA.

Reference

Structural and functional analysis of E6 oncoprotein: insights in the molecular pathways of human papillomavirus-mediated pathogenesis., Nomine Y, Masson M, Charbonnier S, Zanier K, Ristriani T, Deryckere F, Sibler AP, Desplancq D, Atkinson RA, Weiss E, Orfanoudakis G, Kieffer B, Trave G, Mol Cell. 2006 Mar 3;21(5):665-78. PMID:16507364

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