A novel model for the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator

JP Annereau, U Wulbrand, A Vankeerberghen… - FEBS …, 1997 - Wiley Online Library
JP Annereau, U Wulbrand, A Vankeerberghen, H Cuppens, F Bontems, B Tümmler
FEBS letters, 1997Wiley Online Library
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane 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 posttranslational maturation of CFTR. Determination of the three‐dimensional
structure of NBF1 would help to understand this defect. We present a novel model for NBF1
built from the crystal structure of bovine mitochondrial F1‐ATPase protein. This model gives …
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane 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 posttranslational maturation of CFTR. Determination of the three‐dimensional structure of NBF1 would help to understand this defect. We present a novel model for NBF1 built from the crystal structure of bovine mitochondrial F1‐ATPase protein. This model gives a reasonable interpretation of the effect of mutations on the maturation of the protein and, in agreement with the CD data, leads to reconsideration of the limits of NBF1 within CFTR.
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