ABCC7 p.Ile344His
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PMID: 23083715
[PubMed]
El Hiani Y et al: "Tuning of CFTR chloride channel function by location of positive charges within the pore."
No.
Sentence
Comment
78
As shown in Fig. 5, block of both I344H and V345H by Pt(NO2)4 2 was drastically stronger at pH 5.5 than at pH 9.0, with the mean Kd(0) for I344H and V345H being ~13-fold and ~38-fold lower, respectively, at acid pH (Fig. 5 D).
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ABCC7 p.Ile344His 23083715:78:34
status: NEWX
ABCC7 p.Ile344His 23083715:78:140
status: NEW80 In contrast to these large effects of pH on block by Pt(NO2)4 2 , the single-channel conductance of I344H and V345H, as well as that of the WT, were not significantly different at pH 5.5 and pH 9.0 (Fig. 6).
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ABCC7 p.Ile344His 23083715:80:101
status: NEW81 Whereas the conductance of V345H was reduced to ~80% of WT conductance (independently of pH), the conductance of I344H was not significantly different from that of the WT (Fig. 6 C).
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ABCC7 p.Ile344His 23083715:81:113
status: NEW82 Interestingly, whereas the conductance of I344H (at pH 5.5) was not significantly different from that of I344K (p > 0.37; Fig. 2 C), the conductance of V345H (pH 5.5) was ~20% greater than that of V345K (p < 0.002).
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ABCC7 p.Ile344His 23083715:82:42
status: NEW102 In fact, the results of Fig. 6 support the latter explanation, because specifically toggling the positive charge in I344H or V345H by changing the pH did not alter single-channel conductance.
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ABCC7 p.Ile344His 23083715:102:116
status: NEW130 (B) Mean concentration-inhibition relationships for WT (circles), I344H (squares), and V345H (triangles) at intracellular pH 5.5 (left, solid symbols) or 9.0 (right, open symbols) at a membrane potential of 100 mV. Each relationship was fitted according to Eq. 1.
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ABCC7 p.Ile344His 23083715:130:66
status: NEW148 At these two sites, the effect on Pt(NO2)4 2 block could be ascribed unambiguously to an effect of the introduced positive charge, because the mutants I344H and V345H showed Pt(NO2)4 2 block similar to that of WT at pH 9.0, where the histidine side chains are expected to be uncharged, whereas at pH 5.5, which should promote protonation of these side chains, Pt(NO2)4 2 block was drastically strengthened (Fig. 5).
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ABCC7 p.Ile344His 23083715:148:152
status: NEW