Effect of deleting the R domain on CFTR-generated chloride channels.
The cystic fibrosis transmembrane conductance regulator (CFTR), which forms adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, is defective in patients with cystic fibrosis. This protein contains two putative nucleotide binding domains (NBD1 and NBD2) and an R domain. CFTR in which the R domain was deleted (CFTR delta R) conducted chloride independently of the presence of cAMP. However, sites within CFTR other than those deleted also respond to cAMP, because the chloride current of CFTR delta R increased further in response to cAMP stimulation. In addition, deletion of the R domain suppressed the inactivating effect of a mutation in NBD2 (but not NBD1), a result which suggests that NBD2 interacts with the channel through the R domain.
Rich
D P
DP
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Gregory
R J
RJ
Anderson
M P
MP
Manavalan
P
P
Smith
A E
AE
Welsh
M J
MJ
D001665:Binding Sites; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004252:DNA Mutational Analysis; D004553:Electric Conductivity; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000502:physiology*; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D009566:Nitrates / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D009566:Nitrates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP