title: Differential function of the two nucleotide binding domains on cystic fibrosis transmembrane conductance regulator.
abstract: The genetic disease cystic fibrosis is caused by defects in the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). CFTR belongs to the family of ABC transporters. In contrast to most other members of this family which transport substrates actively across a membrane, the main function of CFTR is to regulate passive flux of substrates across the plasma membrane. Chloride channel activity of CFTR is dependent on protein phosphorylation and presence of nucleoside triphosphates. From electrophysiological studies of CFTR detailed models of its regulation by phosphorylation and nucleotide interaction have evolved. These investigations provide ample evidence that ATP hydrolysis is crucial for CFTR gating. It becomes apparent that the two nucleotide binding domains on CFTR not only diverge strongly in sequence, but also in function. Based on previous models and taking into account new data from pre-steady-state experiments, a refined model for the action of nucleotides at two nucleotide binding domains was recently proposed.
authors.affiliation: Max-Planck-Institut für Biophysik, Kennedyallee 70, 60596, Frankfurt/M., Germany.
authors.forename: G
authors.initials: G
authors.lastname: Nagel
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003550:Cystic Fibrosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D010766:Phosphorylation
chemical_list: D018528:ATP-Binding Cassette Transporters; C505032:CFTR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C089765:NUBP1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate