title: Structure and function of the cystic fibrosis transmembrane conductance regulator.
abstract: Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the CFTR gene may result in a defective processing of its protein and alter the function and regulation of this channel. Mutations are associated with different symptoms, including pancreatic insufficiency, bile duct obstruction, infertility in males, high sweat Cl-, intestinal obstruction, nasal polyp formation, chronic sinusitis, mucus dehydration, and chronic Pseudomonas aeruginosa and Staphylococcus aureus lung infection, responsible for 90% of the mortality of CF patients. The gene responsible for the cellular defect in CF was cloned in 1989 and its protein product CFTR is activated by an increase of intracellular cAMP. The CFTR contains two membrane domains, each with six transmembrane domain segments, two nucleotide-binding domains (NBDs), and a cytoplasmic domain. In this review we discuss the studies that have correlated the role of each CFTR domain in the protein function as a chloride channel and as a regulator of the outwardly rectifying Cl- channels (ORCCs).
authors.affiliation: Laboratório de Fisiologia Renal, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. mmorales@biof.ufrj.br
authors.forename: M M
authors.initials: MM
authors.lastname: Morales
authors.forename: M A
authors.initials: MA
authors.lastname: Capella
authors.forename: A G
authors.initials: AG
authors.lastname: Lopes
mesh_terms: D018118:Chloride Channels / Q000502:physiology*; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator