Clues to restoring normal function in gene that causes cystic fibrosis

A recent study publish in Cell has shown that to restore normal function to the mutant gene product that causes Cystic Fibrosis (CF), it is necessary to correct two structural defects. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), the most common mutation being deltaF508, which results in a misfolded version of CFTR. The research team went off the evidence that the effects of the mutation were not limited to the domain of deltaF508, but rather, domain-domain interactions cause another defect. The discovery was that to restore a cell to a normal-like appearance, both structural defects must be corrected simultaneously. "If there are two different folding steps to correct, it is difficult to envision how a single drug could work," explained Gergely Lukacs, who led the study. "The proposed two-step folding model points to the fact that the correction strategy has to be reconsidered."