ABCMdb

PMID: 19761259

Loo TW, Bartlett MC, Clarke DM
Correctors enhance maturation of DeltaF508 CFTR by promoting interactions between the two halves of the molecule.
Biochemistry. 2009 Oct 20;48(41):9882-90., 2009-10-20 [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCC7 p.Val510Cys ABCC7 p.Ala1067Cys Coexpression of ΔF508/N-half and C-half CFTR in the presence correctors VX-325 and corr-4a, however, restored interactions between the two halves. An interaction that was restored was that between NBD1 and TMD2 as the correctors restored cross-linking of mutant ΔF508/NBD1- (V510C)/TMD2(A1067C). Login to comment 48 ABCC7 p.Val510Cys The construction of double-cysteine CFTR mutant ΔF508/V510C- (NBD1)/A1067C(TMD2) in a Cys-less background was described previously (17). Login to comment 78 ABCC7 p.Val510Cys ABCC7 p.Ala1067Cys For example, mature CFTR shows cross-linking between cysteines in TM segment 6 (N-half) and TM segment 12 (C-half) or between cysteines in NBD1 [N-half (V510C)] and ICL4 [C-half (A1067C)], but the immature form of ΔF508 does not (17, 25). Login to comment 101 ABCC7 p.Val510Cys ABCC7 p.Ala1067Cys The black dot indicates the predicted location of an introduced cysteine (A1067C) in TMD2 that will directly cross-link to a cysteine introduced into NBD1 (V510C). Login to comment 174 ABCC7 p.Ala1067Cys To test if correctors VX-325 and corr-4a promoted NBD1-TMD2 interactions in ΔF508 CFTR, mutant ΔF508/V510C(NBD1)/A1067C- (TMD2) was expressed in the presence or absence of the correctors. Login to comment 182 ABCC7 p.Ala1067Cys Expression of ΔF508/V510C(NBD1)/A1067C- (TMD2) in the presence of correctors, however, yielded mature CFTR (180 kDa protein) (Figure 5, right). Login to comment