ABCC7 p.Val232Arg
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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
134
To test if other charged amino acids inhibited maturation, we constructed mutants V232R and V232K.
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ABCC7 p.Val232Arg 24412276:134:82
status: NEW160 We tested if mutations to Val232 that severely inhibited maturation (V232E, V232K, or V232R) could be rescued with other correctors predicted to act as pharmacological chaperones such as 4a [33], VX-809 [19], 2b [35], 5a [12], or VX-325 [36].
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ABCC7 p.Val232Arg 24412276:160:86
status: NEW164 Mutant V232K was rescued with correctors 4a, VX-809 and VX-325 (25-60% mature product) (Fig. 4B and D) while mutant V232R could only be rescued with VX-809 (about 25% mature product) (Fig. 4C and D).
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ABCC7 p.Val232Arg 24412276:164:116
status: NEW165 The V232R mutant may have been difficult to rescue because arginine is the largest and most highly charged amino acid replacement.
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ABCC7 p.Val232Arg 24412276:165:4
status: NEW171 Accordingly, we introduced the V510D suppressor mutation into mutants V232E, V232K, or V232R.
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ABCC7 p.Val232Arg 24412276:171:87
status: NEW175 The V510D suppressor caused a small increase in the amount of V232K mature protein (10%) but no detectable increase was observed in mutant V232R when expressed in the absence of VX-809 (Fig. 5A and B).
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ABCC7 p.Val232Arg 24412276:175:139
status: NEW177 The relative maturation levels achieved using correctors or the V510D suppressor show that the V232E mutation could be more efficiently rescued than the V232K or V232R mutations.
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ABCC7 p.Val232Arg 24412276:177:162
status: NEW188 Fig. 4. Rescue of V232E, V232K, and V232R mutants with correctors.
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ABCC7 p.Val232Arg 24412276:188:36
status: NEW189 Whole cell extracts of cells expressing mutants V232E (A), V232K (B), or V232R (C) in the absence (none) or presence of various correctors were subjected to immunoblot analysis.
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ABCC7 p.Val232Arg 24412276:189:73
status: NEW222 (A) Whole cell extracts of cells expressing CFTR mutants V232E/V510D, V232K/V510D or V232R/ V510D in the absence () or presence (+) of VX-809 or were subjected to immunoblot analysis.
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ABCC7 p.Val232Arg 24412276:222:85
status: NEW285 Fig. 9. Replacement of hydrophobic residues predicted to be close to Val232 with arginine inhibits maturation.
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ABCC7 p.Val232Arg 24412276:285:69
status: NEW