ABCMdb

PMID: 22966013

Tsai MF
CFTR: An ion channel with a transporter-type energy-coupling mechanism.
J Gen Physiol. 2012 Oct;140(4):343-5. Epub 2012 Sep 10., [PubMed]

Sentences

No. Mutations Sentence Comment

25 ABCC7 p.Arg352Cys By mutating residue R352 in the transmembrane domain to cysteine, they created a mutant CFTR channel (R352C-CFTR) that harbors experimentally distinguishable O1 and O2 states not seen in wild-type (WT) channel gating. Login to comment 27 ABCC7 p.Arg352Cys By mutating residue R352 in the transmembrane domain to cysteine, they created a mutant CFTR channel (R352C-CFTR) that harbors experimentally distinguishable O1 and O2 states not seen in wild-type (WT) channel gating. Login to comment 32 ABCC7 p.Arg352Cys A critical issue that has not been addressed by Jih et al. (2012) is to what degree the R352C mutation distorts normal molecular behaviors of CFTR. Login to comment 34 ABCC7 p.Arg352Cys A critical issue that has not been addressed by Jih et al. (2012) is to what degree the R352C mutation distorts normal molecular behaviors of CFTR. Login to comment 35 ABCC7 p.Arg352Cys This allows a qualitative comparison of WT and R352C gating behavior. Login to comment 37 ABCC7 p.Arg352Cys This allows a qualitative comparison of WT and R352C gating behavior. Login to comment 38 ABCC7 p.Arg352Cys Now, the rate constants derived from recording the R352C mutant could provide constraints for the ML method, which can then be applied to examine CFTR kinetic models in an even more satisfactory detail. Login to comment 40 ABCC7 p.Arg352Cys Now, the rate constants derived from recording the R352C mutant could provide constraints for the ML method, which can then be applied to examine CFTR kinetic models in an even more satisfactory detail. Login to comment 48 ABCC7 p.Arg352Cys ABCC7 p.Glu1371Ser The authors then took the story one step further by introducing a catalysis-abolishing mutation E1371S into R352C-CFTR; these hydrolysis-deficient channels now open and close reversibly (C࢐O1࢐C and C࢐O2࢐C), indicating that ATP hydrolysis underlies a unidirectional transition from O1 to O2 (Fig. 1 B). Login to comment 50 ABCC7 p.Arg352Cys ABCC7 p.Glu1371Ser The authors then took the story one step further by introducing a catalysis-abolishing mutation E1371S into R352C-CFTR; these hydrolysis-deficient channels now open and close reversibly (C→O1→C and C→O2→C), indicating that ATP hydrolysis underlies a unidirectional transition from O1 to O2 (Fig. 1 B). Login to comment 51 ABCC7 p.Lys1250Ala ABCC7 p.Glu1371Gln Indeed, unlike ABC transporters, which absolutely require ATPase activity to move substrates, CFTR mutants incapable of catalyzing ATP hydrolysis (e.g., K1250A, D13710N, and E1371Q) exhibit gating transitions with open probabilities comparable to WT (Powe et al., 2002; Vergani et al., 2003). Login to comment 53 ABCC7 p.Lys1250Ala ABCC7 p.Glu1371Gln Indeed, unlike ABC transporters, which absolutely require ATPase activity to move substrates, CFTR mutants incapable of catalyzing ATP hydrolysis (e.g., K1250A, D13710N, and E1371Q) exhibit gating transitions with open probabilities comparable to WT (Powe et al., 2002; Vergani et al., 2003). Login to comment 56 ABCC7 p.Arg352Cys By using the R352C mutation as a tool, now Jih et al. (2012) have the ability to directly quantify the rate constants connecting C, O1, and O2 states, and thus better characterize previously undissectible molecular events, such as ATP hydrolysis (O1࢐O2), at the single molecule level. Login to comment 58 ABCC7 p.Arg352Cys By using the R352C mutation as a tool, now Jih et al. (2012) have the ability to directly quantify the rate constants connecting C, O1, and O2 states, and thus better characterize previously undissectible molecular events, such as ATP hydrolysis (O1→O2), at the single molecule level. Login to comment 60 ABCC7 p.Arg352Cys (C) A single-channel event of R352C-CFTR with three conductance states, acquired with my high-resolution word editor. Login to comment 62 ABCC7 p.Arg352Cys (C) A single-channel event of R352C-CFTR with three conductance states, acquired with my high-resolution word editor. Login to comment