title: Evidence that the C-terminal PB2-binding region of the influenza A virus PB1 protein is a discrete alpha-helical domain.
abstract: The influenza A virus RNA-dependent RNA polymerase is a heterotrimer composed of PB1, PB2 and PA subunits and essential for viral replication. However, little detailed structural information is available for this important enzyme. We show by circular dichroism spectroscopy that polypeptides from the C-terminus of PB1 that are capable of binding efficiently to PB2 fold into stable alpha-helical structures. Structure prediction analysis of this region of PB1 indicates that it likely consists of a three-helical bundle. Deletion of any of the helices abrogated transcriptional function. Thus, PB1 contains a C-terminal alpha-helical PB2-binding domain that is essential for nucleotide polymerization activity.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Poole
authors.forename: Liz
authors.initials: L
authors.lastname: Medcalf
authors.forename: Debra
authors.initials: D
authors.lastname: Elton
authors.forename: Paul
authors.initials: P
authors.lastname: Digard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1