title: Structure of the retinoblastoma protein bound to adenovirus E1A reveals the molecular basis for viral oncoprotein inactivation of a tumor suppressor.
abstract: The adenovirus (Ad) E1A (Ad-E1A) oncoprotein mediates cell transformation, in part, by displacing E2F transcription factors from the retinoblastoma protein (pRb) tumor suppressor. In this study we determined the crystal structure of the pRb pocket domain in complex with conserved region 1 (CR1) of Ad5-E1A. The structure and accompanying biochemical studies reveal that E1A-CR1 binds at the interface of the A and B cyclin folds of the pRb pocket domain, and that both E1A-CR1 and the E2F transactivation domain use similar conserved nonpolar residues to engage overlapping sites on pRb, implicating a novel molecular mechanism for pRb inactivation by a viral oncoprotein.
authors.affiliation: Program in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
mesh_terms: D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D018360:Crystallography, X-Ray; D050684:E2F Transcription Factors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009856:Oncogene Proteins, Viral / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D050684:E2F Transcription Factors; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins