ABCMdb

ABCC7 p.Phe337Tyr

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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

122 ------------------------------------------------------------------------------------------------------------------------ F337Y, a mutation which results in only a small change in amino acid side chain size. Login to comment
134 In order to determine whether the changes in relative anion conductance observed in F337S (Table 1) were associated with the change in selectivity or the change in conductance in this mutant, relative anion conductance was also examined in F337Y (Fig. 8). Login to comment
140 Anion conductance changes observed in F337S are not seen in F337Y Relative Cl¦, Br¦ and F¦ conductances were estimated under symmetrical ionic conditions by macroscopic current variance analysis. Login to comment
144 ------------------------------------------------------------------------------------------------------------------------ (compared with wild-type) in gBrÏgCl and the 710% increase in gFÏgCl, were not reproduced in F337Y (Fig. 8). Login to comment
246 The effects of the mutation F337S on relative anion conductance were not mimicked by another mutation, F337Y, which shows a similarly reduced Cl¦ conductance but unaltered anion selectivity (Fig. 8). Login to comment

PMID: 14610019 [PubMed] Gong X et al: "Mutation-induced blocker permeability and multiion block of the CFTR chloride channel pore."

No. Sentence Comment

4 A mutation in the pore region that alters anion selectivity, F337A, but not another mutation at the same site that has no effect on selectivity (F337Y), had a complex effect on channel block by intracellular Pt(NO2)4 2- ions. Login to comment
6 Current in the presence of Pt(NO2)4 2- increased at very negative voltages in F337A but not wild-type or F337Y, apparently due to relief of block by permeation of Pt(NO2)4 2- ions to the extracellular solution. Login to comment
102 Neither of these effects were observed in another F337 mutant, F337Y, which was blocked in an apparently similar manner as wild-type (Fig. 5, C and E). Login to comment
105 However, when we investigated the block at the most negative voltages that we were able to keep membrane patches (-150 mV) with a low extracellular Cl-concentration (4 mM), we noticed an anomalous voltage-dependent increase in Pt(NO2)4 2--blocked current in F337A but not in wild-type, F337Y or T338A (Fig. 6). Login to comment
106 Under these conditions, the strength of Pt(NO2)4 2- block in wild-type, F337Y, and T338A increases with increasingly negative voltages, eventually leading to a negative slope of the current-voltage relationship in the presence of blocker (Fig. 6 B). Login to comment
116 Thus, at very negative voltages, Pt(NO2)4 2- ions can escape from the F337A channel pore, but apparently not from the pore of wild-type, F337Y or T338A, by passing through the channel and into the extracellular solution-a process previously termed "punchthrough" (Nimigean and Miller, 2002). Login to comment
151 (E) Comparison of the mean blocking effect of 300 ␮M intracellular Pt(NO2)4 2- on wild-type (᭺; fitted as in D) and F337Y (᭹; fitted by Eq. 2 with Kd(0) ϭ 582 ␮M and z␦ ϭ -0.318). Login to comment
189 Previously, we showed that the mutations F337A and F337S, but not F337Y, disrupted the ability of the CFTR channel pore to select between permeant anions on the basis of free energy of hydration (Linsdell et al., 2000) and suggested that F337 contributes to a lyotropic anion "selectivity filter." Login to comment
207 Since this complex blocking behavior is observed in F337A but not in wild-type or F337Y, we suggest that by allowing Pt(NO2)4 2to permeate through the pore, the F337A mutant also allows this blocker to reach a binding site which is normally inaccessible or much less easily accessed. Login to comment

PMID: 10827976 [PubMed] Linsdell P et al: "Molecular determinants of anion selectivity in the cystic fibrosis transmembrane conductance regulator chloride channel pore."

No. Sentence Comment

70 The mutants F337L, F337Y, and I344A gave only modest alterations in anion permeability (Table 1) that led to only slight changes in the anion selectivity sequence (Table 2). Login to comment
74 As described previously for wild-type CFTR (Linsdell and Hanrahan, 1998a), the mutants F337A, F337S, and F337Y all showed negligible Naaf9; permeability (Table 1). Login to comment
77 Both wild-type and F337Y (Fig. 3), as well as F337L, F337W, and I344A (not shown; see Table 2), were able to select for anions that bound water molecules less strongly, consistent with the lyotropic selectivity sequence common to most classes of Clafa; channels (see Introduction). Login to comment
81 Thus the mutant F337Y, which substitutes a similarly sized but polar side chain, has a selectivity that is almost identical to that of wild type. Login to comment
116 Although we cannot rule out this possibility, we feel that the fact that mutations at two adjacent TM6 residues, F337 (this study) and T338 (Linsdell et al., 1998), significantly affect TABLE 1 Relative permeability of intracellular ions in wild-type and mutant CFTR Cld1a; channels Wild type F337A F337S F337L F337Y F337W I344A Cl 1.00 afe; 0.01 (10) 1.00 afe; 0.04 (6) 1.00 afe; 0.08 (3) 1.00 afe; 0.02 (5) 1.00 afe; 0.02 (6) 1.00 afe; 0.03 (5) 1.00 afe; 0.01 (9) Br 1.37 afe; 0.07 (8) 0.60 afe; 0.04 (4)** 0.50 afe; 0.04 (4)** 1.22 afe; 0.04 (5) 1.39 afe; 0.04 (3) 1.12 afe; 0.05 (4)* 1.74 afe; 0.01 (3)* I 0.83 afe; 0.03 (6) 0.23 afe; 0.04 (5)** 0.23 afe; 0.02 (4)** 0.39 afe; 0.01 (3)** 0.69 afe; 0.03 (7)* - 0.99 afe; 0.05 (4)* F 0.103 afe; 0.007 (9) 0.35 afe; 0.01 (4)** 0.43 afe; 0.02 (4)** 0.15 afe; 0.02 (3)* 0.095 afe; 0.009 (3) 0.081 afe; 0.009 (3) 0.075 afe; 0.012 (5)* SCN 3.55 afe; 0.26 (7) 0.97 afe; 0.05 (4)** 0.93 afe; 0.10 (5)** 2.85 afe; 0.20 (4) 3.05 afe; 0.29 (4) 4.42 afe; 0.56 (4) 3.27 afe; 0.30 (5) NO3 1.58 afe; 0.04 (10) 1.30 afe; 0.03 (3)* 1.08 afe; 0.02 (4)** 1.38 afe; 0.03 (4)* 1.43 afe; 0.04 (3) 1.62 afe; 0.03 (3) 1.71 afe; 0.06 (4) ClO4 0.25 afe; 0.01 (8) 0.19 afe; 0.00 (3)* 0.17 afe; 0.03 (4)* 0.23 afe; 0.04 (3) 0.15 afe; 0.01 (4)** - 0.24 afe; 0.02 (3) Formate 0.24 afe; 0.01 (9) 0.27 afe; 0.02 (3) 0.33 afe; 0.03 (4)* 0.35 afe; 0.02 (3)* 0.24 afe; 0.01 (3) - 0.28 afe; 0.01 (3) Acetate 0.091 afe; 0.003 (10) 0.073 afe; 0.004 (3)* 0.12 afe; 0.02 (5) - 0.092 afe; 0.014 (4) - 0.076 afe; 0.007 (3) Naaf9; 0.007 afe; 0.010 (24) 0.001 afe; 0.018 (3) 0.001 afe; 0.021 (5) - 0.002 afe; 0.004 (3) - - Relative permeabilities for different anions present in the intracellular solution under biionic conditions were calculated from macroscopic current reversal potentials (e.g., Fig. 2), according to Eq. 1 (see Materials and Methods). Login to comment
122 TABLE 2 Anion selectivity sequences for wild-type and mutant CFTR Cld1a; channels Wild-type SCNafa; b0e; NO3 afa; b0e; Brafa; b0e; Clafa; b0e; Iafa; b0e; ClO4 afa; b07; form b0e; Fafa; b0e; ace F337A NO3 afa; b0e; Clafa; c56; SCNafa; b0e; Brafa; b0e; Fafa; b0e; form c56; Iafa; b0e; ClO4 afa; b0e; ace F337S NO3 afa; b0e; Clafa; c56; SCNafa; b0e; Brafa; b0e; Fafa; b0e; form b0e; Iafa; b0e; ClO4 afa; b0e; ace F337L SCNafa; b0e; NO3 afa; b0e; Brafa; b0e; Clafa; b0e; Iafa; b0e; form b0e; ClO4 afa; b0e; Fafa; F337Y SCNafa; b0e; NO3 afa; c56; Brafa; b0e; Clafa; b0e; Iafa; b0e; form b0e; ClO4 afa; b0e; Fafa; b07; ace I344A SCNafa; b0e; Brafa; c56; NO3 afa; b0e; Clafa; b07; Iafa; b0e; form b0e; ClO4 afa; b0e; ace b07; Fafa; Sequences were derived from the relative anion permeabilities given in Table 1. form, formate; ace, acetate. Login to comment
158 While the mutants F337L, F337Y, and I344A maintain Eisenman sequence III, both F337A and F337S convert the channel to a relatively strong field strength sequence (Clafa; b0e; Brafa; b0e; Fafa; b0e; Iafa; ; Eisenman sequence V) (Table 2). Login to comment
165 However, SCNafa; permeability is reduced to a similar extent in F337A (hydrophobic) and F337S (polar), but is not altered in F337Y (polar) (Table 1), suggesting that SCNafa; permeability is not influenced by hydrophobic interactions with the large, hydrophobic side chain of F337. Login to comment
168 Thus in wild-type CFTR (and to a similar extent F337L and F337Y), the bulky side chain at position 337 might impede the approach of permeating anions to a nearby anion-attracting group, ensuring relatively weak, long-distance interactions between the anion and this positive site. Login to comment