Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes a chloride channel protein that belongs to the superfamily of ATP binding cassette (ABC) transporters. Phosphorylation by protein kinase A in the presence of ATP activates the CFTR-mediated chloride conductance of the apical membranes. We have identified a novel hydrophilic CFTR binding protein, CAP70, which is also concentrated on the apical surfaces. CAP70 consists of four PDZ domains, three of which are capable of binding to the CFTR C terminus. Linking at least two CFTR molecules via cytoplasmic C-terminal binding by either multivalent CAP70 or a bivalent monoclonal antibody potentiates the CFTR chloride channel activity. Thus, the CFTR channel can be switched to a more active conducting state via a modification of intermolecular CFTR-CFTR contact that is enhanced by an accessory protein.
Wang
S
S
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Yue
H
H
Derin
R B
RB
Guggino
W B
WB
Li
M
M
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D002457:Cell Extracts / Q000032:analysis / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000187:drug effects* / Q000502:physiology
D002352:Carrier Proteins; D002457:Cell Extracts; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator