ABCMdb

ABCC7 p.Arg347Lys

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Publications

PMID: 10026154 [PubMed] Cotten JF et al: "Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge."

No. Sentence Comment

2 Every Arg347 mutation examined, except R347K, had a destabilizing effect on the pore, causing the channel to flutter between two conductance states. Login to comment
24 To better understand the role of Arg-347 in CFTR structure and function, we examined the effect of mutating Arg-347 to cysteine, aspartic acid, glutamic acid, lysine, and leucine on CFTR conductance. Login to comment
25 We examined the cytosolic pH (pHc)-dependent behavior of CFTR-R347H and that of the other residue 347 mutants both with (R347C, R347D, R347E, and R347K) and without (R347L) a pHc-titratable residue. Login to comment
40 Moreover, like CFTR-R347H, all the other residue 347 mutants, except R347K, displayed two pHc-dependent conductance states over a similar pHc range. Login to comment
75 Unexpectedly, all the other variants at residue 347, except R347K, showed two pHc-dependent conductance states over a similar pH range. Login to comment
77 The conservative substitution of Arg-347 by Lys (R347K) showed only a single conductance state and no pHc dependence. Login to comment
82 The all-points histograms (Fig. 1) illustrate qualitatively that as pHc increased, each mutant except R347K spent an increased fraction of time in OL and a correspondingly decreased fraction of time in OB. Login to comment
84 Wild-type CFTR and R347K possess only one predominant conductance state over the pHc range 5.5-7.3 (Fig. 1, data not shown, and Ref. 8). Login to comment
91 Single-channel Conductance of Residue 347 Mutants-To determine whether the residue at position 347 affects single-channel conductance and not merely the conductance state of the channel, we examined the I-V relationship and slope conductance of the mutants with slower pHc-dependent kinetics, R347H and R347E, as well as R347K. Login to comment
94 The single-channel conductance at pHc 6.0 of wild-type CFTR, R347K, and the OB state of R347E and R347H were all very similar (in pS): 7.7 Ϯ 0.4, 8.3 Ϯ 0.6, 7.4 Ϯ 0.4, and 6.9 Ϯ 0.2, respectively (n ϭ 3 for each). Login to comment
119 Single-channel I-V relationships for R347E (OL and OB states), R347H (OL and OB states), R347K, R347D/D924R, and wild-type CFTR at pHc 6.0. n ϭ 2-4 at each data point. Login to comment
177 The OB and OL Conductance States-All the mutants except R347K showed two pH-dependent conductance states. Login to comment

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

No. Sentence Comment

22 Incontrast, R347K-CFTR exhibited permeation properties similar to those of wild-type (WT)-CFTR. Login to comment

PMID: 23709221 [PubMed] Cui G et al: "Two salt bridges differentially contribute to the maintenance of cystic fibrosis transmembrane conductance regulator (CFTR) channel function."

No. Sentence Comment

89 A, representative current samples of WT-, R347A-, R347D-, D924R-, R347K-, and R347D/D924R-CFTR were recorded from excised inside-out patch from Xenopus oocytes with 150 mM Clafa; symmetrical solution in the presence of 1 mM Mg-ATP and 50 nM PKA at VM afd; afa;100 mV (n afd; 4-6 for each mutant). Login to comment
95 R347K-CFTR, retaining the positive charge of arginine, showed behavior similar to WT-CFTR (afa;0.72 afe; 0.02 pA, n afd; 7) but with a slightly larger single channel amplitude (afa;0.89 afe; 0.01 pA, n afd; 4, p b0d; 0.05). Login to comment
99 In all of the Arg347 and Asp924 mutants described above, other than R347K, transitions to the f state did not lead to stable occupancy of that state. Login to comment
109 We therefore hypothesized that Arg347 might also interact with Asp993 to rescue the CFTR channel pore to a stable f state and tested this hypothesis in three double mutants; TABLE 1 Summary of the effects of mutations studied Mutant Main features of open bursts Impact on f state R347A Emphasizes s1 state, brief transitions to s2 and f Can reach f but not stable R347D Emphasizes s1 state, no transitions to s2 and f Cannot reach f D924R Brief transitions to all conductance levels Can reach f but not stable R347K Wild type-like Wild type-like R347D/D924R Emphasizes s2 state, rare and brief transitions to f Can reach f but not stable R352E Opens to all 3 levels; s1 much more stable than in WT, s2 unstable, f unstable Can reach f but not stable D993R Opens to all 3 levels, but none are stable Can reach f but not stable R352E/D993R Wild type-like, with increased transitions to s1 and s2; slightly reduced single-channel conductance Wild type-like R352E/D924R Opens to all 3 levels, but none are stable Can reach f but not stable R347D/D993R Very stable s2; rare and brief transitions to both s1 and f Can reach f but not stable R347A/R352A Opens to all 3 levels; s1 much more stable than in WT, s2 unstable, f unstable Can reach f but not stable R347D/D924R/D993R Opens to all 3 levels; s1 much more stable than in WT, s2 relatively stabilized, f unstable Can reach f but not stable R347D/D924R/R352E/D993R Primarily flickers between s2 and f; s1 much more stable than in WT, slightly reduced single channel conductance Can reach f but not stable FIGURE 3. Login to comment