ABCMdb

ABCC7 p.Glu873Arg

None has been submitted yet.

Publications

PMID: 18421494 [PubMed] Cui G et al: "Mutations at arginine 352 alter the pore architecture of CFTR."

No. Sentence Comment

162 Slope conductances are summarized in Table 1 Table 1 Slope conductancea (in pS) of the f state of WT-CFTR and multiple single and double mutants CFTR n Negative VM Positive VM WT 7 6.82 ± 0.03 6.97 ± 0.06 R352A 6 6.80 ± 0.06 7.85 ± 0.07*, ** R352Q 6 5.29 ± 0.02* 6.28 ± 0.05*, ** R352K 5 6.87 ± 0.03 6.86 ± 0.01 R352E 5 3.78 ± 0.01* 6.03 ± 0.01*, ** R352E/E873R 6 3.84 ± 0.01* 5.64 ± 0.01*, ** R352E/ E1104R 6 4.36 ± 0.01* 5.86 ± 0.02*, ** R352E/D993R 5 5.90 ± 0.02* 6.44 ± 0.01*, ** D993R 7 8.27 ± 0.05* 7.13 ± 0.07** a Slope conductance indicates single-channel conductance calculated from 0 to +100 mV (positive VM) or to -100 mV (negative VM) by linear regression * P B 0.001 compared to the equivalent slope conductance in WT-CFTR, ** P B 0.001 compared to the slope conductance in the same mutant at negative VM reflects the loss of anion binding properties within the core of the permeation pathway, which contributes to the tight binding of SCN (Smith et al. 1999). Login to comment
199 We studied the conductance properties of CFTR channels bearing the following mutations: R352E, R352E/E873R, R352E/ D993R and R352E/E1104R. Login to comment
201 Three of these mutants, R352E-, R352E/E873R- and R352E/E1104R-CFTR, exhibited instability of the open state, in which the amplitudes of the s1, s2 and f conductance states were very similar between the three mutants. Login to comment
204 R352E-, R352E/ E873R- and R352E/E1104R-CFTR exhibited significant outward rectification, while WT-CFTR did not (Table 1). Login to comment
208 If D993 served as the interaction partner of R352, we would expect that block of R352E/D993R-CFTR would be similar to that 0.4 pA 2 s 0.4 pA 2 s 0.2 pA 2 s 0.2 pA 2 s c s1 s2 f c s1 s2 f c s1 s2 f c f R352E R352E/E873R R352E/E1104R R352E/D993R 0 4000 #ofevents 0.0 -0.4 -0.8 0.0 -0.4 -0.8 3000 #ofevents 0 #ofevents 0.0 -0.4 -0.8 3000 0 Currents (pA) 0.0 -0.4 0 2500#ofevents -0.8 fc s1 s2 s1 s2 s1 s2 0.4 pA 2 s 0.4 pA 2 s 0.2 pA 2 s 0.2 pA 2 s c s1 s2 f c s1 s2 f c s1 s2 f c f R352E R352E/E873R R352E/E1104R R352E/D993R 0.4 pA 2 s 0.4 pA 2 s 0.4 pA 2 s 0.4 pA 2 s 0.2 pA 2 s 0.2 pA 2 s 0.2 pA 2 s 0.2 pA 2 s c s1 s2 f c s1 s2 f c s1 s2 f c f R352E R352E/E873R R352E/E1104R R352E/D993R B C D A 0 4000 #ofevents 0.0 -0.4 -0.8 0 4000 #ofevents 0.0 -0.4 -0.8 0.0 -0.4 -0.8 3000 #ofevents 0 0.0 -0.4 -0.8 3000 #ofevents 0 #ofevents 0.0 -0.4 -0.8 3000 0 Currents (pA) #ofevents 0.0 -0.4 -0.8 3000 0 #ofevents 0.0 -0.4 -0.8 3000 0 Currents (pA) 0.0 -0.4 0 2500#ofevents -0.8 fc s1 s2 s1 s2 s1 s2 Fig. 7 Single-channel current tracings of R352E-CFTR and double mutants from excised inside-out patches (left) and resulting all-points amplitude histograms (right) under the same experimental conditions as in Fig. 1. Login to comment
232 Hence, it is likely that MTSEA+ modified one (or more) of the endogenous cysteines, which B WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R mV -100 -50 50 100 -0.8 -0.4 0.4 0.8 pA 100 ms 0.2 nA A WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R mV -100 -50 50 100 -0.8 -0.4 0.4 0.8 pA WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R WT-CFTR R352E/D993R R352E R352E/E873R R352E/E1104R mV -100 -50 50 100 -0.8 -0.4 0.4 0.8 pA 100 ms 0.2 nA Fig. 8 The double mutant R352E/D993R-CFTR recovers WT-like channel behavior. Login to comment
233 (A) Single channel i-V relationships are shown for full conductance states of WT-, R352E-, R352E/E873R-, R352E/ E1104R- and R352E/D993R-CFTR. Login to comment
258 Second, we identified the interaction partner as D993 by use of double mutants; R352E/E873R-CFTR and R352E/E1104R-CFTR exhibited permeation properties similar to those of R352E-CFTR, while R352E/D993R-CFTR behaved more like WT-CFTR. Login to comment