Fig 1.
E6 structure and LXXLL interactions.
A. Ribbon diagram of HPV16 E6 bound to the LXXLL motif from E6AP [20]. The amino-terminal zinc-binding domain (16E6-N in green) is connected by an alpha helix (yellow) to the E6-C zinc-binding domain at the bottom (blue). The helical LXXLL peptide from the cellular E6AP ubiquitin ligase (salmon color) resides in a deep 16E6 pocket. B. Divergent E6 proteins have conserved folds. Despite the limited homology (30% identity), the evolutionary divergence of human and bovine hosts, and different interacting cellular protein targets, superimposition of HPV16 E6 (green) and BPV1 E6 (red) structures demonstrates the conservation of the overall fold of E6 and its interaction with the cellular protein–derived LXXLL peptides. The paxillin (PXN) and E6AP-LXXLL peptides in the structure are colored with their respective E6 protein, and known interacting LXXLL peptide sequences are shown to the right (hydrophobic side chains in blue and acidic side chains in purple).