FRONTIERS IN RESEARCH ON CYSTIC-FIBROSIS - UNDERSTANDING ITS MOLECULAR AND CHEMICAL BASIS AND RELATIONSHIP TO THE PATHOGENESIS OF THE DISEASE

In recent years a new family of transport proteins called ABC transpor ters has emerged. One member of this novel family, called CFTR (cystic fibrosis transmembrane conductance regulator), has received special a ttention because of its association with the disease cystic fibrosis ( CF). This is an inherited disorder affecting about 1 in 2000 Caucasian s by impairing epithelial ion transport, particularly that of chloride . Death may occur in severe cases because of chronic lung infections, especially by Pseudomonas aeruginosa, which cause a slow decline in pu lmonary function. The prospects of ameliorating the symptoms of CF and even curing the disease were greatly heightened in 1989 following the cloning of the CFTR gene and the discovery that the mutation (Delta F 508), which causes mast cases of CF, is localized within a putative AT P binding/ATP hydrolysis domain. The purpose of this introductory revi ew in this minireview series is to summarize what we and others have l earned during the past eight years about the structure and function of the first nucleotide binding domain (NBF1 or NBD1) of the CFTR protei n and the effect thereon of disease-causing mutations. The relationshi p of these new findings to the pathogenesis of CF is also discussed.