Conformational states of CFTR associated with channel gating: the role ATP binding and hydrolysis.
CFTR is a member of the traffic ATPase superfamily and a Cl- ion channel that appears to require ATP hydrolysis for gating. Analysis of single CFTR Cl- channels reconstituted into planar lipid bilayers revealed the presence of two open conductance states that are connected to each other and to the closed state by an asymmetric cycle of gating events. We show here that the transition between the two open conductance states is directly coupled to ATP hydrolysis by one of the consensus nucleotide-binding folds, designated NBF2. Moreover, the transition between the closed state and one of the open states is linked to the binding of ATP. This analysis permits real-time visualization of conformational changes associated with a single cycle of ATP hydrolysis by a single protein molecule and suggests a model describing a role for ATP in CFTR gating.
Gunderson
K L
KL
Department of Biological Sciences and Biophysics Program, Stanford University, California 94305-5020, USA.
Kopito
R R
RR
D000255:Adenosine Triphosphate / Q000378:metabolism*; D018118:Chloride Channels / Q000737:chemistry / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004553:Electric Conductivity; D006801:Humans; D006868:Hydrolysis; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D008861:Microsomes / Q000378:metabolism; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D008274:Magnesium