Papillomavirus E6 oncoproteins

- E6 oncoproteins have two zinc-structured domains connected by an alpha helix.
- The E6 protein fold is highly conserved in evolution.
- E6 makes a pocket that binds to LXXLL peptides on target proteins.
- E6 biological activities are mediated by E6-LXXLL interaction.

Papillomaviruses induce benign and malignant epithelial tumors, and the viral E6 oncoprotein is essential for full transformation. E6 contributes to transformation by associating with cellular proteins, docking on specific acidic LXXLL peptide motifs found on these proteins. This review examines insights from recent studies of human and animal E6 proteins that determine the three-dimensional structure of E6 when bound to acidic LXXLL peptides. The structure of E6 is related to recent advances in the purification and identification of E6 associated protein complexes. These E6 protein-complexes, together with other proteins that bind to E6, alter a broad array of biological outcomes including modulation of cell survival, cellular transcription, host cell differentiation, growth factor dependence, DNA damage responses, and cell cycle progression.