Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins

Katia Zanier (1) , Sebastian Charbonnier (1) , Abdellahi Ould M'Hamed Ould Sidi , Alastair G Mcewen (2) , Maria Giovanna Ferrario (3) , Pierre Poussin-Courmontagne (2) , Vincent Cura (4) , Nicole Brimer , Khaled Ould Babah (1) , Tina Ansari , Isabelle Muller (1) , Roland H Stote , Jean Cavarelli , Scott Vande Pol , Gilles Trave (1)

1 BSC - Biotechnologie et signalisation cellulaire
2 Structural Biology and Genomics Platform [Illkirch]
3 Lancaster University
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

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.

Domaines: Biologie structurale [q-bio.BM]; Virologie

Katia Zanier, Sebastian Charbonnier, Abdellahi Ould M'Hamed Ould Sidi, Alastair G Mcewen, Maria Giovanna Ferrario, et al.. Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins. Science, 2013, 339 (6120), pp.694-698. ⟨10.1126/science.1229934⟩. ⟨hal-03049110⟩