ABCMdb

PMID: 9379169

Linsdell P, Tabcharani JA, Hanrahan JW
Multi-Ion mechanism for ion permeation and block in the cystic fibrosis transmembrane conductance regulator chloride channel.
J Gen Physiol. 1997 Oct;110(4):365-77., [PubMed]

Sentences

No. Mutations Sentence Comment

45 ABCC7 p.Arg347Asp three-site model was also able to predict all of the effects of SCN- on CFTR permeation previously described for both wild-type and R347D CFTR (Tabcharani et al., 1993). Login to comment 156 ABCC7 p.Arg347Asp SCN- block is not seen in a pore mutant form of CFTR, R347D (Tabcharani et al., 1993), suggesting that this amino acid may contribute to the SCN- binding site. Login to comment 157 ABCC7 p.Arg347Asp Since R347D also has a Cl- conduc- tance of only ‫%05ف‬ of wild-type CFTR, it was suggested Figure 10. Comparison of experimental data with theoretical values predicted by the three-site model. Login to comment 170 ABCC7 p.Arg347Asp ABCC7 p.Arg347Asp Three-Site, Multi-Occupancy Model for R347D CFTR Block of CFTR by internal SCN-, and the anomalous mole fraction dependence of conductance seen in Cl-/ SCN- mixtures are lost in the low conductance pore mutant R347D CFTR (Tabcharani et al., 1993). Login to comment 171 ABCC7 p.Arg347Asp We wanted to see if the three-site model developed above for SCN- could be modified to describe the permeation properties of R347D CFTR. Login to comment 173 ABCC7 p.Arg347Asp As shown in Fig. 13, specific changes in the height of the second barrier and both adjacent wells near the cytoplasmic end of both the Cl- and SCN- energy profiles were able to reproduce the reduction in Cl- con- ductance (Fig. 13 C), loss of blockade by 10 mM internal SCN- (Fig. 13 C), and the loss of anomalous mole fraction behavior (Fig. 13 D) seen in R347D CFTR. Login to comment 192 ABCC7 p.Arg347Asp A three-site energy profile for R347D CFTR. Login to comment 193 ABCC7 p.Arg347Asp (A and B) Best fit energy profiles for Cl- (A) and SCN- (B) in wild-type (solid lines) and R347D CFTR (dashed lines). Login to comment 194 ABCC7 p.Arg347Asp (C) The three-site model of Fig. 13, A and B predicts the reduced conductance of R347D in symmetrical 150 mM NaCl (᭺) and the lack of block by 10 mM intracellular SCN- (᭹). Login to comment 195 ABCC7 p.Arg347Asp (D) Loss of anomalous mole fraction dependence of conductance in R347D. Login to comment 207 ABCC7 p.Arg347Asp The fact that specific modifications of the model can also reproduce the effects of the pore mutation R347D (Fig. 13) also suggest it may serve as a useful starting point in structure-function studies. Login to comment 214 ABCC7 p.Ser341Ala The mutation S341A also severely reduces channel conductance, suggesting that this amino acid also interacts with permeating Cl- ions (McDonough et al., 1994). Login to comment