ABCC7 p.Thr1122Cys

[switch to full view]
Comments [show]
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.
X
ABCC7 p.Thr1122Cys 19381710:71:228
status: NEW
Login to comment

72 Of 21 cysteine mutants studied, only six significantly altered I-V relationship shape in the absence of external MTS reagents (Fig. 3a), with S1118C, T1121C, T1122C, G1127C and A1136C all causing significant inward rectification and V1129C showing outward rectification.
X
ABCC7 p.Thr1122Cys 19381710:72:158
status: NEW
Login to comment

84 Unitary currents at depolarized voltages were significantly decreased in S1118C, T1121C, T1122C and G1127C and significantly increased in V1129C (Fig. 5b).
X
ABCC7 p.Thr1122Cys 19381710:84:89
status: NEW
Login to comment

85 This resulted in changes in the shape of the i-V relationship, causing inward rectification in the case of S1118C, T1121C, T1122C and G1127C and outward rectification in the case of V1129C (Figs. 4b, 5c).
X
ABCC7 p.Thr1122Cys 19381710:85:123
status: NEW
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).
X
ABCC7 p.Thr1122Cys 19381710:91:80
status: NEW
Login to comment

118 Four mutations (S1118C, T1121C, T1122C, G1127C) led to significant decreases in unitary current amplitude (Fig. 5b), which were relatively strongly affected by MTS modification-in each case conductance was further decreased by reaction with MTSES and increased to near wild-type levels by MTSET (Fig. 9a).
X
ABCC7 p.Thr1122Cys 19381710:118:32
status: NEW
Login to comment

125 a Example single-channel currents carried by wild-type, S1118C, T1121C, T1122C and V1129C, at membrane potentials of ?60 (top) and -60 (bottom) mV.
X
ABCC7 p.Thr1122Cys 19381710:125:72
status: NEW
Login to comment

130 Block was not significantly altered in either T1122C or G1127C (data not shown).
X
ABCC7 p.Thr1122Cys 19381710:130:46
status: NEW
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).
X
ABCC7 p.Thr1122Cys 19381710:133:105
status: NEW
Login to comment

158 Of the seven mutants that were functionally modified by MTS reagents, five (S1118C, T1121C, T1122C, G1127C, V1129C) also showed significantly altered unitary current amplitude in the absence of MTS modification (Figs. 4, 5).
X
ABCC7 p.Thr1122Cys 19381710:158:92
status: NEW
Login to comment

161 a S1118C (d), T1121C (j), T1122C (), G1127C (h); b V1129C (m), I1131C (r), I1132C (.).
X
ABCC7 p.Thr1122Cys 19381710:161:26
status: NEW
Login to comment

183 We speculate that one group of reactive mutants (S1118C, T1121C, T1122C, G1127C) is located relatively deep in the pore from the outside and that the other (V1129C, Fig. 11 Thiocyanate permeability of mutants.
X
ABCC7 p.Thr1122Cys 19381710:183:65
status: NEW
Login to comment

188 In this scenario, charge-neutral mutations deeper in the pore (S1118C, T1121C, T1122C, G1127C) (Fig. 9a) disrupt Cl- movement in the pore in a nonelectrostatic fashion, leading to reduced unitary currents at depolarized voltages, as described previously for TM6 mutations (McDonough et al. 1994; Linsdell et al. 1998; Linsdell 2001a).
X
ABCC7 p.Thr1122Cys 19381710:188:79
status: NEW
Login to comment

200 Mutations S1118C, T1122C and G1127C also altered the anion selectivity of CFTR, significantly increasing SCN- per- meability (Fig. 11), which is consistent with changes in pore structure and function.
X
ABCC7 p.Thr1122Cys 19381710:200:18
status: NEW
Login to comment

PMID: 23955087 [PubMed] Wang W et al: "Relative contribution of different transmembrane segments to the CFTR chloride channel pore."
No. Sentence Comment
122 Previously it was shown that S1118C, T1121C, and T1122C-but not F1116C, I1117C, I1119C, or L1120C-are accessible to externally applied MTS reagents [10].
X
ABCC7 p.Thr1122Cys 23955087:122:49
status: NEW
Login to comment

187 The proposed relative alignment of TMs 6 and 11 presented in Fig. 9a is consistent not only with the pattern of MTSES accessibility from different sides of the membrane, but also with previous data showing that disulfide bonds can form between T338C and S1118C, and between R334C and T1122C, in open channels [43].
X
ABCC7 p.Thr1122Cys 23955087:187:284
status: NEW
Login to comment