ABCMdb

ABCC7 p.Phe374Ala

None has been submitted yet.

Publications

PMID: 23924900 [PubMed] Ren HY et al: "VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1."

No. Sentence Comment

72 Despite the severe biogenic defects exhibited by F374A-CFTR, L375A-CFTR, the double mutation F374A/L375A-CFTR (Figure 3A), F374A-CFTR 380, and L375A-CFTR 380 (Figure 3B), VX-809 almost completely suppressed the biogenic defects caused by the F374A and L375A mutations at the 5-bc;M concentration that maximally suppressed folding defects in F508del-CFTR (Figure 3, A and B). Login to comment
96 Interestingly, the positive effect of S2 and S3 on F508del-CFTR biogenesis was abolished by the F374A mutation, as VX-809 could not drive high-level accumulation of the folded C-band of F374A/S2/F508del-CFTR or F374A/S3/F508del-CFTR. Login to comment
97 In addition, the F374A mutation hindered VX-809 from suppressing folding defects in F508del-CFTR. Login to comment
98 In experiments with CFTR, the S2 and S3 mutations by themselves increased C-band accumulation almost twofold, and this effect was blocked by F374A (Figure 5C). Login to comment
99 Yet, in contrast to results with F508del-CFTR, VX-809 restored accumulation of the C-form of F374A/S2-CFTR and F374A/S3-CFTR to levels of S2 CFTR and S3 CFTR under control conditions. Login to comment
104 The folding defect caused by F374A is efficaciously corrected by VX-809 (Figure 3), but the F374A mutation blocks VX-809 action on F508del-CFTR. Login to comment
105 In addition, F374A also blocks the positive effect of S mutations on CFTR and F508del-CFTR biogenesis. Login to comment
153 (D) F374A L375A CFTR exhibits a folding defect that is not efficaciously suppressed by VX-809. Login to comment
157 CFTR 380 F374A ࢞371-375 % of Cont. Login to comment
162 380- CFTR 380 Trypsin (ug/ml) 25 20 15- - - - + Vehicle +VX-809 * CFTR 370 CFTR 370 2520- 15- CFTR 380 * +Vehicle + VX-809 ** ** + _ Wt _ VX-809 + _ + _ F374A L375A F374A L375A + _ ࢞371-375 Tub- C- BC- 100 4 108 6 115 2 12 8 7 B31 24 28 23 24 25 27 22 19 CFTR %-Wt C-band C. VX-809 0 5 10 15 _ ࢞371-375 -C -B CFTR Wt %-Wt 100 4 6 5 2 C-band 25 12 18 11 8 + CFTR 3800 25 2 1 7 3 0 25 2 1 7 3 D. Login to comment
175 (B) Mutation of F374A hinders the ability of misfolding suppressor mutations S2 and S3 to increase the efficacy of VX-809 on F508del-CFTR. Login to comment
176 (C) Mutation of F374A hinders the ability of S2 and S3 to increase accumulation of the folded C-band of CFTR. Login to comment
182 Vehicle VX-809 + + _ _ + + _ _ + + _ _ + + _ _ + + _ _ + + _ _ F508 F508 F374 F508 F374A S2 F508 F374A S3 F508 S2 F508 S3 + _ CFTR Tub- -C -B Wt C-100 1 12 2 4 3 4 1 3 1 42 8 51 B40 31 60 40 61 32 64 33 43 28 49 25 43 Vehicle VX-809 + + _ _ + + _ _ + + _ _ + + _ _ + + _ _ + _ F374A F374A S2 F374A S3 S2 S3 Tub- CFTR -C -B Wt C-100 9 80 8 158 7 162 136 182 163 225 B28 14 18 25 19 26 15 11 5 13 5 A. Login to comment
219 Soluble lysates were obtained by centrifugation at 20,000 &#d7; g combined mutation of F374A and L375A but efficaciously suppresses folding defects caused by each individual mutation. Login to comment