Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Two salt bridges differentially contribute to the maintenance of cystic fibrosis transmembrane conductance regulator (CFTR) channel function.
Cui G
,
Freeman CS
,
Knotts T
,
Prince CZ
,
Kuang C
,
McCarty NA
.
???displayArticle.abstract???
Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg(352)-Asp(993) and Arg(347)-Asp(924), that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg(347) not only interacts with Asp(924) but also interacts with Asp(993). The tripartite interaction Arg(347)-Asp(924)-Asp(993) mainly contributes to maintaining a stable s2 open subconductance state. The Arg(352)-Asp(993) salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg(352) and Asp(993), channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle.
Alexander,
Cystic fibrosis transmembrane conductance regulator: using differential reactivity toward channel-permeant and channel-impermeant thiol-reactive probes to test a molecular model for the pore.
2009, Pubmed,
Xenbase
Alexander,
Cystic fibrosis transmembrane conductance regulator: using differential reactivity toward channel-permeant and channel-impermeant thiol-reactive probes to test a molecular model for the pore.
2009,
Pubmed
,
Xenbase
Aubin,
Positive charges at the intracellular mouth of the pore regulate anion conduction in the CFTR chloride channel.
2006,
Pubmed
Bai,
Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7).
2011,
Pubmed
Bai,
Dual roles of the sixth transmembrane segment of the CFTR chloride channel in gating and permeation.
2010,
Pubmed
Cotten,
Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge.
1999,
Pubmed
Craven,
C-terminal movement during gating in cyclic nucleotide-modulated channels.
2008,
Pubmed
,
Xenbase
Craven,
Salt bridges and gating in the COOH-terminal region of HCN2 and CNGA1 channels.
2004,
Pubmed
,
Xenbase
Cui,
Differential contribution of TM6 and TM12 to the pore of CFTR identified by three sulfonylurea-based blockers.
2012,
Pubmed
,
Xenbase
Cui,
Mutations at arginine 352 alter the pore architecture of CFTR.
2008,
Pubmed
,
Xenbase
Dawson,
Cystic fibrosis transmembrane conductance regulator. Permeant ions find the pore.
1997,
Pubmed
DeCaen,
Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor.
2011,
Pubmed
DeCaen,
Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation.
2008,
Pubmed
DeCaen,
Sequential formation of ion pairs during activation of a sodium channel voltage sensor.
2009,
Pubmed
Drumm,
Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes.
1991,
Pubmed
,
Xenbase
Fuller,
The block of CFTR by scorpion venom is state-dependent.
2005,
Pubmed
,
Xenbase
Fuller,
State-dependent inhibition of cystic fibrosis transmembrane conductance regulator chloride channels by a novel peptide toxin.
2007,
Pubmed
,
Xenbase
Gnann,
Cystic fibrosis transmembrane conductance regulator degradation depends on the lectins Htm1p/EDEM and the Cdc48 protein complex in yeast.
2004,
Pubmed
Holstead,
Functional differences in pore properties between wild-type and cysteine-less forms of the CFTR chloride channel.
2011,
Pubmed
Hong,
Electrostatic couplings in OmpA ion-channel gating suggest a mechanism for pore opening.
2006,
Pubmed
Kunzelmann,
Inhibition of epithelial Na+ currents by intracellular domains of the cystic fibrosis transmembrane conductance regulator.
1997,
Pubmed
,
Xenbase
Lee,
Principal pathway coupling agonist binding to channel gating in nicotinic receptors.
2005,
Pubmed
Marchais,
Interaction of permeant ions with channels activated by acetylcholine in Aplysia neurones.
1979,
Pubmed
Mense,
In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer.
2006,
Pubmed
,
Xenbase
Mornon,
Molecular models of the open and closed states of the whole human CFTR protein.
2009,
Pubmed
Mornon,
Atomic model of human cystic fibrosis transmembrane conductance regulator: membrane-spanning domains and coupling interfaces.
2008,
Pubmed
Moroni,
Flip-flopping salt bridges gate an ion channel.
2006,
Pubmed
Pusch,
Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel.
1995,
Pubmed
Riordan,
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
1989,
Pubmed
Riordan,
CFTR, a channel with the structure of a transporter.
1992,
Pubmed
Schneggenburger,
Coupling of permeation and gating in an NMDA-channel pore mutant.
1997,
Pubmed
,
Xenbase
Serohijos,
Phenylalanine-508 mediates a cytoplasmic-membrane domain contact in the CFTR 3D structure crucial to assembly and channel function.
2008,
Pubmed
Swenson,
K+ channels close more slowly in the presence of external K+ and Rb+.
1981,
Pubmed
Wang,
Alignment of transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore.
2011,
Pubmed
Yang,
Stabilization of ion selectivity filter by pore loop ion pairs in an inwardly rectifying potassium channel.
1997,
Pubmed
,
Xenbase
Zhang,
Determination of the functional unit of the cystic fibrosis transmembrane conductance regulator chloride channel. One polypeptide forms one pore.
2005,
Pubmed
Zhang,
State-dependent chemical reactivity of an engineered cysteine reveals conformational changes in the outer vestibule of the cystic fibrosis transmembrane conductance regulator.
2005,
Pubmed
