ABCC7 p.Phe1111Ser
| CF databases: |
c.3331T>C
,
p.Phe1111Leu
(CFTR1)
?
,
|
| Predicted by SNAP2: | A: N (53%), C: N (72%), D: D (80%), E: D (71%), G: D (63%), H: D (71%), I: N (82%), K: D (75%), L: N (72%), M: N (61%), N: D (66%), P: D (80%), Q: D (66%), R: D (75%), S: D (53%), T: N (53%), V: N (87%), W: D (71%), Y: D (63%), |
| Predicted by PROVEAN: | A: N, C: N, D: D, E: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: N, V: N, W: D, Y: N, |
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[hide] Interaction between permeation and gating in a put... Biophys J. 2000 Jul;79(1):298-313. Zhang ZR, McDonough SI, McCarty NA
Interaction between permeation and gating in a putative pore domain mutant in the cystic fibrosis transmembrane conductance regulator.
Biophys J. 2000 Jul;79(1):298-313., [PMID:10866956]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel with distinctive kinetics. At the whole-cell level, CFTR currents in response to voltage steps are time independent for wild type and for the many mutants reported so far. Single channels open for periods lasting up to tens of seconds; the openings are interrupted by brief closures at hyperpolarized, but not depolarized, potentials. Here we report a serine-to-phenylalanine mutation (S1118F) in the 11th transmembrane domain that confers voltage-dependent, single-exponential current relaxations and moderate inward rectification of the macroscopic currents upon expression in Xenopus oocytes. At steady state, the S1118F-CFTR single-channel conductance rectifies, corresponding to the whole-cell rectification. In addition, the open-channel burst duration is decreased 10-fold compared with wild-type channels. S1118F-CFTR currents are blocked in a voltage-dependent manner by diphenylamine-2-carboxylate (DPC); the affinity of S1118F-CFTR for DPC is similar to that of the wild-type channel, but blockade exhibits moderately reduced voltage dependence. Selectivity of the channel to a range of anions is also affected by this mutation. Furthermore, the permeation properties change during the relaxations, which suggests that there is an interaction between gating and permeation in this mutant. The existence of a mutation that confers voltage dependence upon CFTR currents and that changes kinetics and permeation properties of the channel suggests a functional role for the 11th transmembrane domain in the pore in the wild-type channel.
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No. Sentence Comment
33 Preparation of oocytes and cRNA CFTR was subcloned into the pALTER vector (Promega), and the S1118F, S1118A, and S1118F/F1111S mutations were made using the Promega Altered Sites protocol (McDonough et al., 1994).
X
ABCC7 p.Phe1111Ser 10866956:33:120
status: NEW118 To determine whether this imposed pattern was the source of relaxations in S1118F-CFTR, due to introduction of another bulky residue, the double mutation S1118F/F1111S was constructed.
X
ABCC7 p.Phe1111Ser 10866956:118:161
status: NEW