A NOVEL MODEL FOR THE FIRST NUCLEOTIDE-BINDING DOMAIN OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

Cystic fibrosis is caused by mutations in the cystic fibrosis transmem brane conductance regulator (CFTR) gene. The most frequent mutation is the deletion of F508 in the first nucleotide binding fold (NBF1). It induces a perturbation in the folding of NBF1, which impedes posttrans lational maturation of CFTR. Determination of the three-dimensional st ructure of NBF1 would help to understand this defect. We present a nov el model for NBF1 built from the crystal structure of bovine mitochond rial F-1-ATPase protein. This model gives a reasonable interpretation of the effect of mutations on the maturation of the protein and, in ag reement with the CD data, leads to reconsideration of the limits of NB F1 within CFTR. (C) 1997 Federation of European Biochemical Societies.