FIGURE 3:

CFTR amino acids 370–380 are required for folding of MSD1 to a conformation stabilized by VX-809. (A) Deletion of residues 371–375 causes a folding defect in CFTR that is insensitive to VX-809. (B) Mutation of residues 374 and 375 causes folding defects in CFTR 380 that are suppressed by VX-809. (C) CFTR 380, but not CFTR 370, folds to a trypsin-resistant conformation that is stabilized by VX-809. (D) F374A L375A CFTR exhibits a folding defect that is not efficaciously suppressed by VX-809. Levels of indicated forms of CFTR expressed in HEK293 cells were detected by Western blot with N-terminal–tail antibody. (C) Cells were lysed with PBS that contained 1% Triton X-100 and the indicated concentration of trypsin, and digestions were carried out on ice for 15 min. Unless otherwise noted, VX-809 was 5 μM.