Journal
SCIENCE
Volume 339, Issue 6120, Pages 694-698Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1229934
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Funding
- CNRS
- Universite de Strasbourg
- INSERM
- European Commission SPINE2-Complexes project [LSHG-CT-2006-031220]
- Association pour la Recherche contre le Cancer (ARC) [3171]
- Agence Nationale de la Recherche [ANR-MIME-2007 EPI-HPV-3D]
- NIH [R01CA134737, CA120352, CA134737, CA08093]
- ANR
- ARC
- College Doctoral Europeen
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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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