title: Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade.
abstract: The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder. The crystal structure of the catalytic hect domain of E6AP reveals a bilobal structure with a broad catalytic cleft at the junction of the two lobes. The cleft consists of conserved residues whose mutation interferes with ubiquitin-thioester bond formation and is the site of Angelman syndrome mutations. The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3.
authors.affiliation: Cellular Biochemistry and Biophysics Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: E
authors.initials: E
authors.lastname: Kinnucan
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Beaudenon
authors.forename: P M
authors.initials: PM
authors.lastname: Howley
authors.forename: J M
authors.initials: JM
authors.lastname: Huibregtse
authors.forename: N P
authors.initials: NP
authors.lastname: Pavletich
mesh_terms: D000595:Amino Acid Sequence; D017204:Angelman Syndrome / Q000235:genetics; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D014452:Ubiquitins; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D003545:Cysteine