correctors enhance maturation of deltaf508 cftr by promoting interactions between the two halves of the molecule deletion of phe508 in cystic fibrosis transmembrane conductance regulator deltaf508 cftr causes cystic fibrosis cftr consists of two homologous halves with each containing a nucleotidebinding domain nbd and a transmembrane domain tmd deltaf508 cftr appears to be trapped in an incompletely folded state small molecules correctors promote folding of deltaf508 cftr with relatively low efficiency understanding the mechanism of repair may lead to the development of more effective correctors here we tested the effect of correctors and the deltaf508 mutation on interactions between the halves of cftr when expressed as separate polypeptides glycosylation of chalf cftr was defective when expressed alone as a mixture of core and unglycosylated proteins was detected coexpression of chalf cftr with either wildtype nhalf or deltaf508nhalf cftr however increased the amount of coreglycosylated protein but only coexpression with wildtype nhalf promoted maturation of chalf cftr endo h resistant this suggested that the deltaf508 mutation inhibited some interactions between nhalf and chalf cftrs interaction of a52tagged wildtype nhalf or deltaf508nhalf cftr with histidinetagged chalf cftr was then followed by nickelchelate chromatography coexpression of a52tagged wildtype nhalf or deltaf508nhalf cftr with histidinetagged chalf cftr resulted in the wildtype nhalf cftr but not deltaf508nhalf cftr protein being retained on the column coexpression of deltaf508nhalf and chalf cftr in the presence correctors vx325 and corr4a however restored interactions between the two halves an interaction that was restored was that between nbd1 and tmd2 as the correctors restored crosslinking of mutant deltaf508nbd1v510ctmd2a1067c therefore correctors promote proper interactions between the two halves of cftr