Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins.

Date publication

février 2013

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CAVARELLI Jean , Dr STOTE Roland , Dr TRAVE Gilles

Tous les auteurs :
Zanier K, Charbonnier S, Sidi AO, McEwen AG, Ferrario MG, Poussin-Courmontagne P, Cura V, Brimer N, Babah KO, Ansari T, Muller I, Stote RH, Cavarelli J, Vande Pol S, Trave G

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/23393263

Résumé

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.

Référence

Science. 2013 Feb 8;339(6120):694-8