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Updated: May 14, 2026

In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 23, 2010
Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins
Katia Zanier1, Sebastian Charbonnier, Abdellahi Ould M'hamed Ould Sidi
1Biotechnologie et Signalisation Cellulaire UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP 10413, F-67412 Illkirch, France.
Abstract:
E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses in vertebrates, including cervical cancer in humans. E6 proteins target many host proteins by specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus E6 proteins bound to LxxLL peptides from the focal adhesion protein paxillin and the ubiquitin ligase E6AP, respectively. In both E6 proteins, two zinc domains and a linker helix form a basic-hydrophobic pocket, which captures helical LxxLL motifs in a way compatible with other interaction modes. Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins.
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