title: The amino-terminal portion of CFTR forms a regulated Cl- channel.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel consists of two motifs (each containing a membrane-spanning domain [MSD] and a nucleotide-binding domain [NBD]) linked by an R domain. We tested the hypothesis that one MSD-NBD motif could form a Cl- channel. The amino-terminal portion of CFTR (D836X, which contains MSD1, NBD1, and the R domain) formed Cl- channels with conductive properties identical to those of CFTR. However, channel regulation differed. Although phosphorylation increased activity, channels opened without phosphorylation. MgATP stimulated D836X more potently than CFTR and may interact at more than one site. These data and migration of D836X on sucrose density gradients suggest that D836X may function as a multimer. Thus, the amino-terminal portion of CFTR contains all of the structures required to build a regulated Cl- channel.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: D N
authors.initials: DN
authors.lastname: Sheppard
authors.forename: L S
authors.initials: LS
authors.lastname: Ostedgaard
authors.forename: D P
authors.initials: DP
authors.lastname: Rich
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001704:Biopolymers; D002499:Centrifugation, Density Gradient; D018118:Chloride Channels / Q000737:chemistry / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D016297:Mutagenesis, Site-Directed
chemical_list: D001704:Biopolymers; C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D000242:Cyclic AMP