ABSTRACT
Although the spectrum of clinical manifestations is quite wide, it has been generally believed that an underlying basis of cystic fibrosis (CF) is abnormal regulation of epithelial ion and fluid transport (1). Primary sequence analysis of the CF gene suggests that its protein product, the cystic fibrosis transmembrane conductance regulator (CFTR), is an integral membrane protein containing structural domains similarly present in proteins with known transport functions (2,3). CFTR is a member of the traffic ATPase or ATP binding cassette (ABC transporter) superfamily of proteins. It is composed of two membrane-associated domains, each with six putative transmembrane helices, two nucleotide binding domains (NBDs), and a large cytoplasmic R (regulatory) domain that contains numerous consensus sequences for kinase phosphorylation (2,3). Cystic fibrosis is caused by mutations in CFTR. The disease is usually manifested as exocrine pancreatic insufficiency, an increase in sweat Cl concentration, and airway disease. Airway disease leads to progressive lung dysfunction, which is currently the major cause of morbidity and is responsible for 95% of CF mortality.
