ABCMdb

ABCC7 p.Ile1131Cys

None has been submitted yet.

Publications

PMID: 19381710 [PubMed] Fatehi M et al: "Novel residues lining the CFTR chloride channel pore identified by functional modification of introduced cysteines."

No. Sentence Comment

71 As described previously for modification of cysteines introduced into TM6 (Fatehi and Linsdell 2008) and the extracellular loop between TMs 1 and 2 (Zhou et al. 2008), MTSET and MTSES altered the IREL-V shape in S1118C, T1121C, T1122C, G1127C, V1129C, I1131C and I1132C. Login to comment
75 As described above (Fig. 2), six mutants had I-V relationships that were sensitive to both MTSET and MTSES and only one (I1131C) was altered by MTSET but not MTSES. Login to comment
82 In contrast, I1131C and I1132C did not significantly affect the form of either the i-V relationship (Fig. 4b) or the I-V relationship (Fig. 3a). Login to comment
86 No changes in i-V shape were observed for I1131C or I1132C. Login to comment
91 Indeed, changes in unitary current amplitude were observed in S1118C, T1121C, T1122C, G1127C, V1129C, I1131C and I1132C, but not wild-type, when MTS reagents were included in the pipette solution (Fig. 6). Login to comment
114 Note that the rectification ratio in six cysteine mutants is significantly affected by both MTSET and MTSES (indicated by asterisks), whereas in a seventh (I1131C) it is significantly altered by MTSET but not by MTSES voltages as an indicator, Fig. 8 shows that MTS reagents had charge-dependent effects on i-V relationship shape that broadly mirrored those observed in the macroscopic I-V relationships (see Fig. 3c). Login to comment
119 In contrast, the other three mutations (V1129C, I1131C, I1132C) led to no change or even a slight increase in unitary current amplitude (Fig. 5b) and more minor effects of MTS modification, resulting in no change or a small decrease in amplitude with MTSES and increases in amplitude to levels above wild-type with MTSET (Fig. 9b). Login to comment
124 Under these conditions, SCN- block was significantly strengthened in I1132C (at hyperpolarized and depolarized voltages), S1118C (at hyperpolarized voltages), T1121C and V1129C (at depolarized voltages) and I1131C (at very depolarized voltages only) Fig. 4 Single-channel currents carried by cysteine mutant forms of CFTR. Login to comment
133 Under these conditions, SCN- permeability was significantly increased in S1118C and (to a lesser extent) T1122C and G1127C and unaltered in T1121C, V1129C, I1131C and I1132C (Fig. 11). Login to comment
161 a S1118C (d), T1121C (j), T1122C (), G1127C (h); b V1129C (m), I1131C (r), I1132C (.). Login to comment
187 * Significant difference from wild-type (P \ 0.05) I1131C, I1132C) represents mutations at the outermost mouth of the pore. Login to comment
191 Chloride conductance was further reduced by MTSES modification at these sites, indicating the detrimental effect of depositing a negative charge within the permeation pathway. Cysteine substitution at the outer mouth of the pore (V1129C, I1131C, I1132C) (Fig. 9b) had somewhat different effects. Login to comment

PMID: 21796338 [PubMed] Qian F et al: "Functional arrangement of the 12th transmembrane region in the CFTR chloride channel pore based on functional investigation of a cysteine-less CFTR variant."

No. Sentence Comment

90 A similar lack of effect following prolonged (>5 min) exposure to such high concentrations of both MTSES and MTSET was also observed in ten out of 19 cysteine-substituted mutants tested (I1131C, I1132C, L1133C, T1134C, L1135C, A1136C, M1137C, I1139C, L1143C, and A1146C). Login to comment
126 Previous work from our group suggested that externally applied MTS reagents could modify cysteines only in the outermost part of TM12, namely, I1131C and I1132C [11]; these same cysteines were insensitive to internally applied MTS reagents (Fig. 2), again consistent with impermeability to these reagents. Login to comment

PMID: 22352759 [PubMed] Norimatsu Y et al: "Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore."

No. Sentence Comment

177 It is noteworthy that in several cases (e.g., I1131C) application of MTSES- , which carries a net negative charge, led to an increase in macroscopic conductance. Login to comment

PMID: 22923500 [PubMed] Norimatsu Y et al: "Locating a Plausible Binding Site for an Open Channel Blocker, GlyH-101, in the Pore of the Cystic Fibrosis Transmembrane Conductance Regulator."

No. Sentence Comment

151 We also studied the reaction of I1131C CFTR with MTSES- . Login to comment
154 In fact, no occlusion of I1131C was observed with 10 µM GlyH-101, despite more than 80% block of the I1131C CFTR current. Login to comment
155 The rate of reaction between MTSES- and I1131C CFTR was actually somewhat greater in the presence of GlyH-101 (Figure 7A). Login to comment
156 The reaction rates of charged reagents with I1131C CFTR would be influenced by relative positions of nearby charges, which may change slightly in the event of binding of GlyH-101. Login to comment
159 The presence of negative charges near I1131 is consistent with the observed slow reaction of I1131C CFTR with MTSES- (20 M-1 sec-1 ; Figure 7) which is more than 100-fold less than that seen for a Cys at 338 (3.3 x 103 M-1 sec-1 ; Figure 6). Login to comment
160 As reported previously (Norimatsu et al., 2012) the macroscopic conductance of I1131C CFTR was increased by depositing the negatively charged sulfonic acid group via reaction with MTSES- . Login to comment
161 This result is most likely a reflection of an increase in the open probability of I1131C CFTR channels similar to that observed for R352C CFTR by Bai et al., (2010). Login to comment
234 We also studied the reaction of the I1131C CFTR with MTSESafa; . Login to comment
237 No occlusion of I1131C was observed with 10 òe;M GlyH-101, despite more than 80% blockade of the I1131C CFTR current. Login to comment
238 The rate of reaction between MTSESafa; and the I1131C CFTR was actually somewhat greater in the presence of GlyH-101 (Fig. 7A). Login to comment
239 The rates of reactions of charged reagents with the I1131C CFTR would be influenced by the relative positions of nearby charges, which might change slightly upon GlyH-101 binding. Login to comment
242 The presence of negative charges near Ile1131 is consistent with the observed slow reaction of the I1131C CFTR with MTSESafa; (20 Mafa;1 safa;1 ) (Fig. 7), which is more than 100-fold less than the rate seen with a cysteine at position 338 (3.3 afb; 103 Mafa;1 safa;1 ) (Fig. 6). Login to comment
243 As reported previously (Norimatsu et al., 2012), the macroscopic conductance of the I1131C CFTR was increased by deposition of the negatively charged sulfonic acid group through reaction with MTSESafa; . Login to comment
244 This result is most likely a reflection of an increase in the open probability of I1131C CFTR channels, similar to that observed for the R352C CFTR (Bai et al., 2010). Login to comment
273 A, time courses of the reactions of the I1131C CFTR with 1 mM MTSESafa; in the presence and absence of 10 òe;M GlyH-101. Data points represent mean afe; S.E.M. (n afd; 3). Login to comment
274 Covalent labeling of the I1131C CFTR with MTSESafa; resulted in increases in conductance. Login to comment
278 The EC50 at 0 mV for GlyH-101 blockade for the I1131C CFTR was 0.86 afe; 0.016 òe;M (n afd; 3). Login to comment