ABCMdb

ABCC7 p.Ser1118Ala

None has been submitted yet.

Publications

PMID: 11179391 [PubMed] Linsdell P et al: "Relationship between anion binding and anion permeability revealed by mutagenesis within the cystic fibrosis transmembrane conductance regulator chloride channel pore."

No. Sentence Comment

254 Interestingly, S1118 in TM11 has been suggested to occupy a position similar to that of T338 in TM6, and the mutations S1118A and S1118F cause small alterations in anion permeability (Zhang et al. 2000). Login to comment

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

201 Previously, SCN- permeabil- ity was shown to be significantly decreased in S1118F but unaltered in S1118A (Zhang et al. 2000). Login to comment

PMID: 7522483 [PubMed] McDonough S et al: "Novel pore-lining residues in CFTR that govern permeation and open-channel block."

No. Sentence Comment

78 Affinity and Voltage Dependence for Block of CFTR Variants by DPC Construct TM Ko( - 100) (PM) 0 I-V Relation n Properties Wild type Wild type low [Cl-], (10 mM) K335E 6 K335F 6 T338A 6 T339A 6 S341A 6 S341T 6 S1118A 11 T1134A 12 T1134F 12 S1141A 12 Triple 6,12 276 f 14 181 f 13" 303 -t 14 351 * 15' 220 * 14 284 * 47 1251 f 116a 530 f 80" 243 * 37 230 * 20 74 * 3" 220 * 13 325 * 26b 0.41 f 0.01 0.32 f 0.02" 0.42 f 0.01 0.42 f 0.02 0.36 f 0.02" 0.44 * 0.12 0.49 * 0.03" 0.35 f 0.09 0.40 f 0.02 0.35 * 0.02" 0.41 f 0.01 0.42 f 0.03 0.21 * O.Ol",b Linear, E,,, = -8 f 1 mV Ere\ = +48+2mV Inward rectification Linear Linear Linear Strong inward rectification Inward rectification Linear Linear Linear Linear Strong inward rectification Affinity for DPC was determined empirically at -100 mV, from whole-cell currents measured in the presence of 200 uM DPC (see Experimental Procedures). Login to comment

PMID: 10866956 [PubMed] Zhang ZR et al: "Interaction between permeation and gating in a putative pore domain mutant in the cystic fibrosis transmembrane conductance regulator."

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). Login to comment
125 These relaxations are not seen in S1118A channels (not shown). Login to comment
128 In addition, mutation of S1118 to alanine (S1118A-CFTR) did not cause relaxations. Login to comment
180 Instead, currents in oocytes expressing WT-, S1118F-, or S1118A-CFTR channels were elicited by stepping for 75 ms from the holding potential of afa;30 mV to a series of test potentials between afa;140 and af9;80 mV in af9;20 mV increments. Login to comment
206 S1118A-CFTR channels did not indicate time dependence with this protocol (not shown). Login to comment
235 Data are shown for both instantaneous currents and steady-state currents for WT and S1118F-CFTR (Fig. 8, A and B) or S1118A-CFTR (Fig. 8, C and D). Login to comment
236 In Clafa; -containing solutions, before anion substitutions were made, there was a significant difference (p afd; 0.047) between instantaneous and steady-state reversal potentials in S1118F-CFTR (Table 2) compared to the WT (Table 1), but not in S1118A-CFTR. Login to comment
239 The ability of the large anions (acetate, gluconate, glutamate, and isethionate) to gain access to the pore is altered by mutations S1118A and S1118F, as indicated by mild to significant changes in relative permeabilities for these anions compared to that in WT channels. Login to comment
242 S1118A-CFTR exhibited reduced relative permeabilities for all of the large anions and for perchlorate. Login to comment
250 Relative conductances were generally less affected in S1118A-CFTR than in S1118F-CFTR. Login to comment
251 In contrast, mutation S1118A had the greatest effects on PX/PCl relationships, particularly for the large polyatomic anions (Fig. 8, C and D). Login to comment
252 FIGURE 8 Selectivity data for WT CFTR as compared to S1118F-CFTR (A and B) and S1118A-CFTR (C and D). Login to comment
260 &#a7; p b0d; 0.01 for S1118F-CFTR or p afd; 0.02 for S1118A-CFTR. Login to comment
263 Nor does relative permeability for S1118F-CFTR (Fig. 8 A) or S1118A-CFTR (Fig. 8 C) show any time dependence. Login to comment
267 As shown in Fig. 8 D, there was also a statistically significant time dependence of relative conductance to perchlorate for S1118A-CFTR (p afd; 0.02). Login to comment
284 TABLE 2 Selectivity in S1118F-CFTR and S1118A-CFTR Ion S1118F S1118A Erev (mV) PX/PCl GX/GCl Erev (mV) PX/PCl GX/GCl SCN afa;40.97 afe; 1.20* 1.84 afe; 0.08* 0.57 afe; 0.02* afa;56.44 afe; 0.93 2.59 afe; 0.09 0.20 afe; 0.01 NO3 afa;32.83 afe; 1.69 1.30 afe; 0.06 0.95 afe; 0.02 afa;37.35 afe; 0.87 1.21 afe; 0.04 0.88 afe; 0.01 Br afa;28.28 afe; 1.32 1.07 afe; 0.03 0.88 afe; 0.03* afa;34.53 afe; 0.85 1.12 afe; 0.02 0.77 afe; 0.01 Cl afa;26.14 afe; 1.59* 1.0 1.0 afa;30.63 afe; 0.64 1.0 1.0 I afa;8.46 afe; 1.14 0.52 afe; 0.03* 0.38 afe; 0.03* afa;10.35 afe; 1.26 0.39 afe; 0.01 0.27 afe; 0.05 Acetate 39.64 afe; 1.77* 0.05 afe; 0.01* 0.12 afe; 0.01* 23.24 afe; 1.83* 0.09 afe; 0.01* 0.50 afe; 0.01* Glutamate 23.93 afe; 3.61* 0.16 afe; 0.01* 0.23 afe; 0.01* 19.59 afe; 1.07* 0.09 afe; 0.01* 0.49 afe; 0.01* 0.32 afe; 0.01I * Isethionate 20.24 afe; 3.62* 0.14 afe; 0.03 0.25 afe; 0.02* 23.71 afe; 0.99* 0.09 afe; 0.01* 0.48 afe; 0.01 ClO4 afa;6.42 afe; 1.57* 0.42 afe; 0.02* 0.18 afe; 0.01 27.29 afe; 1.36* 0.06 afe; 0.01* 0.12 afe; 0.01* 0.14 afe; 0.01I * Gluconate 28.26 afe; 3.29* 0.12 afe; 0.02 0.20 afe; 0.01* 20.03 afe; 1.04* 0.10 afe; 0.01* 0.50 afe; 0.01* 0.27 afe; 0.01I * Ions are listed in the same order as in Table 1. Login to comment
345 Similarly, S1118A did not affect block by DPC (McDonough et al., 1994). Login to comment
346 However, both S1118A-CFTR and S1118F-CFTR altered the selectivity behavior of the pore, suggesting that this position may contribute to the pore walls. Login to comment
348 In contrast, mutation S1118A exhibited the greatest effects on relative permeabilities, especially for the large anions. Login to comment
377 Similarly, the current relaxations are not due to disruption of a putative interaction between S1118 and another amino acid, because no relaxations were observed for S1118A-CFTR. 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

150 In addition, possible additive effects of reducing the side chain volumes of these two nearby residues was investigated using a T338A/S1118A double mutant. Login to comment
153 In contrast, S1118A had no effect on conductance, while S1118Q and S1118V were associated with Fig. 7 Thiocyanate permeability of mutants. Login to comment
155 The depolarizing (rightward) shift in the current reversal potential indicates an increased PSCN/PCl in the T338A/S1118A double mutant. Login to comment
158 The hypolarizing (leftward) shift in the current reversal potential indicates an increased Pacetate/PCl in the T338A/S1118A double mutant. Login to comment
163 The double mutant T338A/S1118A had a similarly elevated conductance that was not significantly different from that of T338A alone (P>0.75; Fig. 5). Login to comment
167 Block by intracellular Au(CN)2 - was also significantly weakened in S1118A, S1118T, and T1115A compared to wild type, especially at hyperpolarized membrane potentials (Fig. 6); however, no apparent "U"-shape to the fractional current-voltage relationship was observed (Fig. 6b). Login to comment
168 Interestingly, block of the T338A/S1118A double mutant was slightly weaker than for T338A alone (Fig. 6c, d), suggesting that these two mutations might have additive effects on Au(CN)2 - binding in the pore. Login to comment
180 As proposed previously for TM6 residue T338 [42], the channel is shown as being in an "outward facing" configuration when closed (with T1115 and S1118 accessible from the outside), and switching to an "inward facing" configuration on opening (with T1115 and S1118 accessible from the inside) S1118A and T1115A, although this increase was much less than that observed in T338A (Fig. 7b). Login to comment
181 Interestingly, SCN- permeability was further increased in the T338A/S1118A double mutant (Fig. 7). Login to comment
183 Acetate permeability was slightly increased in S1118A and T1115A, but not significantly changed in S1118Q or S1118V (Fig. 8b). Login to comment
184 Again, the increase in acetate permeability seen in T338A was significantly augmented in the T338A/S1118A mutation (Fig. 8), suggesting an additive effect of these two mutations on organic anion permeability. Login to comment
207 The effects of the S1118A mutation on permeant anion (Au(CN)2 - ) binding (Fig. 6), permeability of the lyotropic SCN- anion (Fig. 7), and permeability of the organic acetate anion (Fig. 8) were qualitatively similar to, but generally smaller than, those of T338A, and in fact similar effects were seen in T1115A. Login to comment
208 Neither S1118A nor T1115A significantly altered single channel conductance, although introduction of larger amino acid side chains in S1118Q and S1118V led to very small decreases in conductance (Fig. 5). Login to comment
211 Reduction of side chain volume in S1118A and T1115A, like T338A, led to an increase in the relative permeability of the small organic anion acetate, consistent with an increase in the apparent diameter of the narrowest region of the pore [25, 26]; however, introduction of side chains with larger volume (S1118Q, S1118V) did not lead to a decrease in acetate permeability (Fig. 8). Login to comment
214 Most striking here were a significantly increased permeability of the T338A/S1118A double mutant both to SCN- (Fig. 7) and to acetate (Fig. 8). Login to comment
215 Permeability of small lyotropic anions like SCN- might be influenced by interactions throughout the pore [18, 38] or might be determined predominantly at a localized "selectivity filter" [18, 24] and so the apparently additive effects of the T338A and S1118A mutations is difficult to interpret in terms of the relative roles or locations of these two residues. Login to comment
216 Permeability of large anions such as acetate is thought to be determined predominantly by steric factors at the narrowest part of the pore [25], and so the increase in acetate permeability in T338A/S1118A compared to either mutation alone might be considered evidence that these two mutations impact the dimensions of a common, narrow region of the pore. Login to comment
217 One possible reason contributing to the minor functional effects observed in these experiments is that S1118A (and T1115A) might be considered relatively conservative mutations leading to only small changes in amino acid side chain volume. Login to comment
219 Previously, the S1118C mutation was shown to decrease conductance at positive voltages, leading to inward rectification of both the single channel and macroscopic current-voltage relationships [10], and although this would be considered a very conservative mutation (one oxygen atom replaced by sulfur) this effect was not reproduced in S1118A, S1118Q or S1118 (Fig. 5). Login to comment