title: Sequence homologies between nucleotide binding regions of CFTR and G-proteins suggest structural and functional similarities.
abstract: Sequence homology between the alpha-subunits of G-proteins and other GTP-binding proteins and certain regions within the nucleotide binding domains (NBDs) of cystic fibrosis transmembrane conductance regulator (CFTR) indicates that these protein structures may be similar. A sequence alignment of the NBDs of CFTR and NBDs from other membrane transporters, forms the basis of a structural model. This model predicts that one of the conserved sequences GGQR, within which a number of CF mutations occur, forms part of the nucleotide binding pocket and serves as an ON/OFF conformational switch as observed in GTP binding proteins. Furthermore, based on subtle sequence differences between the first and second NBDs of CFTR and from structure-activity data, we suggest that the nucleotide binding site environments of the two NBDs are different.
authors.affiliation: Department of Biotherapeutic Product Development, Genzyme Corporation, Framingham, MA 01701, USA.
authors.forename: P
authors.initials: P
authors.lastname: Manavalan
authors.forename: D G
authors.initials: DG
authors.lastname: Dearborn
authors.forename: J M
authors.initials: JM
authors.lastname: McPherson
authors.forename: A E
authors.initials: AE
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018118:Chloride Channels / Q000737:chemistry*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019204:GTP-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019204:GTP-Binding Proteins