title: Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins.
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.
authors: Biotechnologie et Signalisation Cellulaire UMR 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard Sébastien Brant, BP 10413, F-67412 Illkirch, France.
authors: Katia
authors: K
authors: Zanier
authors: Sebastian
authors: S
authors: Charbonnier
authors: Abdellahi Ould M'hamed Ould
authors: AO
authors: Sidi
authors: Alastair G
authors: AG
authors: McEwen
authors: Maria Giovanna
authors: MG
authors: Ferrario
authors: Pierre
authors: P
authors: Poussin-Courmontagne
authors: Vincent
authors: V
authors: Cura
authors: Nicole
authors: N
authors: Brimer
authors: Khaled Ould
authors: KO
authors: Babah
authors: Tina
authors: T
authors: Ansari
authors: Isabelle
authors: I
authors: Muller
authors: Roland H
authors: RH
authors: Stote
authors: Jean
authors: J
authors: Cavarelli
authors: Scott
authors: S
authors: Vande Pol
authors: Gilles
authors: G
authors: Travé
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D052688:Bovine papillomavirus 1; D018360:Crystallography, X-Ray; D052162:Human papillomavirus 16; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017354:Point Mutation; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D051419:Paxillin; D010446:Peptide Fragments; D012097:Repressor Proteins; C059269:protein E6, Bovine papillomavirus; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
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