title: Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport.
abstract: The ATP-binding cassette (ABC) superfamily of transport systems now includes over thirty proteins that share extensive sequence similarity and domain organization. This superfamily includes the well characterized periplasmic binding protein-dependent uptake systems of prokaryotes, bacterial exporters, and eukaryotic proteins including the P-glycoprotein associated with multidrug resistance in tumours (MDR), the STE6 gene product that mediates export of yeast a-factor mating pheromone, pfMDR that is implicated in chloroquine resistance of the malarial parasite, and the product of the cystic fibrosis gene (CFTR). Here we present a tertiary structure model of the ATP-binding cassettes characteristic of this class of transport system, based on similarities between the predicted secondary structures of members of this family and the previously determined structure of adenylate kinase. This model has implications for both the molecular basis of transport and cystic fibrosis and provides a framework for further experimentation.
authors.affiliation: Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Hyde
authors.forename: P
authors.initials: P
authors.lastname: Emsley
authors.forename: M J
authors.initials: MJ
authors.lastname: Hartshorn
authors.forename: M M
authors.initials: MM
authors.lastname: Mimmack
authors.forename: U
authors.initials: U
authors.lastname: Gileadi
authors.forename: S R
authors.initials: SR
authors.lastname: Pearce
authors.forename: M P
authors.initials: MP
authors.lastname: Gallagher
authors.forename: D R
authors.initials: DR
authors.lastname: Gill
authors.forename: R E
authors.initials: RE
authors.lastname: Hubbard
authors.forename: C F
authors.initials: CF
authors.lastname: Higgins
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D011487:Protein Conformation; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D000255:Adenosine Triphosphate