title: A novel model for the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator.
abstract: 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.
authors.affiliation: Laboratoire de RMN, DCSO, Ecole Polytechnique, Palaiseau, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Annereau
authors.forename: U
authors.initials: U
authors.lastname: Wulbrand
authors.forename: A
authors.initials: A
authors.lastname: Vankeerberghen
authors.forename: H
authors.initials: H
authors.lastname: Cuppens
authors.forename: F
authors.initials: F
authors.lastname: Bontems
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
authors.forename: V
authors.initials: V
authors.lastname: Stoven
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D003001:Cloning, Molecular; D017124:Conserved Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005091:Exons; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D011487:Protein Conformation; D017510:Protein Folding; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: C505032:CFTR protein, human; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006180:Proton-Translocating ATPases