ABCC7 p.Gln207Leu
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PMID: 17516627
[PubMed]
Wehbi H et al: "Role of the extracellular loop in the folding of a CFTR transmembrane helical hairpin."
No.
Sentence
Comment
143
ments suggest that TM3/4 migration patterns are not simple functions of charge: (i) The double mutant Q207L/V232D migrates identically to WT, while V232D migrates significantly faster than WT (33).
X
ABCC7 p.Gln207Leu 17516627:143:102
status: NEW
PMID: 17949679
[PubMed]
Wehbi H et al: "Positional dependence of non-native polar mutations on folding of CFTR helical hairpins."
No.
Sentence
Comment
160
While some mutants do contain a change in charge vs. WT, previous work from our laboratory has established that CFTR TM3/4 migration patterns are not simple functions of charge: (i) WT TM3/4 and the double mutant Q207L/V232D the same migration rates while V232D migrates significantly faster than WT [20]; (ii) Asp substitutions at 20 different positions along TM4 between residues 221 and 241 produce TM3/4 hairpins that migrate 3-12% faster than WT [22]; if introduction of a single negative charge was the dominating effect, all 20 mutants should display similar migration rates.
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ABCC7 p.Gln207Leu 17949679:160:213
status: NEW161 In the present work, Q207N/V232E-TM3/4 migrates faster than TM3/4-V232D (Fig. 1b) although they each have one added negative charge vs. WT.
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ABCC7 p.Gln207Leu 17949679:161:213
status: NEW
PMID: 15209503
[PubMed]
Choi MY et al: "Non-native interhelical hydrogen bonds in the cystic fibrosis transmembrane conductance regulator domain modulated by polar mutations."
No.
Sentence
Comment
112
To confirm the role of Q207 as the "unique" polar partner for Asp side chains along TM4, we prepared a library of 21 TM3/4 mutants designated XD/Q207L, which has the same net charge as XD (where X is any positional D mutant in TM4) but eliminates Q207 as a possible polar partner for D mutants in TM4.
X
ABCC7 p.Gln207Leu 15209503:112:145
status: NEW113 These mutants were found uniformly to display the same migration rate as the wt, as shown for selected XD/Q207L constructs in Figure 4.
X
ABCC7 p.Gln207Leu 15209503:113:106
status: NEW137 Our observations that interhelical H-bonds are strong determinants of helical hairpin folding can be viewed in the context of studies by Faham et al. which indicate that TM-TM packing forces are dominant over H-bonds in a series FIGURE 4: SDS-PAGE analysis for selected knockout XD/Q207L mutants.
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ABCC7 p.Gln207Leu 15209503:137:282
status: NEW138 The D mutants in TM4 migrate faster than the wild-type construct, while the knockout mutants (with Q207L) retain the wt migration rate due to the fact that the polar partner in TM3 has been eliminated.
X
ABCC7 p.Gln207Leu 15209503:138:99
status: NEW140 All 21 TM4 D mutants with Q207L retained the wt migration rate.
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ABCC7 p.Gln207Leu 15209503:140:26
status: NEW
PMID: 24412276
[PubMed]
Loo TW et al: "The cystic fibrosis V232D mutation inhibits CFTR maturation by disrupting a hydrophobic pocket rather than formation of aberrant interhelical hydrogen bonds."
No.
Sentence
Comment
23
The Q207L mutation did not rescue V232D because Q207L showed about 50% maturation in the presence of corrector VX-809 while V232D/Q207A could no longer be rescued.
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ABCC7 p.Gln207Leu 24412276:23:4
status: NEWX
ABCC7 p.Gln207Leu 24412276:23:48
status: NEW97 The Q207L mutation had previously been reported to abolish hydrogen bond interactions with V232D in TM3/4 helix-loop-helix fragments [24].
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ABCC7 p.Gln207Leu 24412276:97:4
status: NEW100 The V232D, V232D/Q207A, V232D/Q207L, and V232D/Q207C mutants were then expressed in the presence or absence of corrector VX-809 to test for maturation.
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ABCC7 p.Gln207Leu 24412276:100:30
status: NEW104 By contrast, none of the Gln207 mutations rescued V232D CFTR (Fig. 1B and C) as no mature CFTR was observed when mutants V232D/Q207A, V232D/Q207L, or V232D/Q207C were expressed in the presence or absence of VX-809 (Fig. 1B).
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ABCC7 p.Gln207Leu 24412276:104:140
status: NEW107 Mutations to Gln207 inhibit CFTR maturation Since V232D but not mutants V232D/Q207A, V232D/Q207L, or V232D/Q207C could be rescued with VX-809 (Fig. 1B), we tested if maturation of CFTR was also sensitive to changes to Gln207 in a wild-type background.
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ABCC7 p.Gln207Leu 24412276:107:91
status: NEW117 the Q207A, Q207L or Q207C changes.
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ABCC7 p.Gln207Leu 24412276:117:11
status: NEW182 It was observed that in the absence of VX-809, the V510D mutation significantly improved the maturation of Q207L, Q207C, Q207E, Q207N and Q207S (Fig. 6A and B).
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ABCC7 p.Gln207Leu 24412276:182:107
status: NEW183 Mature CFTR was the major product in Q207N/V510D (90% mature product) while mutants Q207L/V510D, Q207C/V510D, Q207E/V510D, and Q207S/V510D showed modest levels of mature CFTR (about 20-40% mature).
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ABCC7 p.Gln207Leu 24412276:183:84
status: NEW184 In the presence of corrector VX-809 however, the amount of mature CFTR in mutants V510D/Q207A V510D/Q207L, V510D/Q207C, V510D/Q207E, V510D/Q207F and V510D/Q207S were significantly increased (25-85% mature product).
X
ABCC7 p.Gln207Leu 24412276:184:100
status: NEW280 They showed that the migration pattern of mutant V232D/Q207L in SDS-PAGE gels resembled that of the wild-type fragment.
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ABCC7 p.Gln207Leu 24412276:280:55
status: NEW284 Although mutants such as A207A, Q207L and Q207C could be rescued with corrector VX-809 (Fig. 2), the V232D mutation appeared to have an effect that was independent of that of Gln207 since mutants Q207A/V232D, Q207L/V232D and Q207C/V232D could no longer be rescued by VX-809 (Fig. 1B).
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ABCC7 p.Gln207Leu 24412276:284:32
status: NEWX
ABCC7 p.Gln207Leu 24412276:284:209
status: NEW