Science (American Association for the Advancement of Science), 2013-02, Vol.339 (6120), p.694-698
2013
Details
- Autor(en) / Beteiligte
- Titel
- Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins
- Ist Teil von
- Science (American Association for the Advancement of Science), 2013-02, Vol.339 (6120), p.694-698
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1229934Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3899395
- Format
- –
- Schlagworte
- Adhesion, Amino Acid Motifs, Amino Acid Sequence, Biochemistry, Molecular Biology, Bovine papillomavirus, Bovine papillomavirus 1, Cancer, Cellular biology, Cervical cancer, Crystal structure, Crystallography, X-Ray, Gene expression, Human, Human papillomavirus, Human papillomavirus 16, Humans, Hydrophobic and Hydrophilic Interactions, Life Sciences, Mammals, Microbiology and Parasitology, Models, Molecular, Molecular Dynamics Simulation, Molecular Sequence Data, Oncogene Proteins, Viral - chemistry, Oncogene Proteins, Viral - genetics, Oncogene Proteins, Viral - metabolism, Paxillin - chemistry, Paxillin - metabolism, Peptide Fragments - chemistry, Peptide Fragments - metabolism, Peptides, Pocket, Point Mutation, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Proteins, Repressor Proteins - chemistry, Repressor Proteins - genetics, Repressor Proteins - metabolism, Structural Biology, Ubiquitin-Protein Ligases - chemistry, Ubiquitin-Protein Ligases - metabolism, Virology, Zinc