ATPASE ACTIVITY OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

The gene mutated in cystic fibrosis codes for the cystic fibrosis tran smembrane conductance regulator (CFTR), a cyclic AMP-activated chlorid e channel thought to be critical for salt and water transport by epith elial cells. Plausible models exist to describe a role for ATP hydroly sis in CFTR channel activity; however, biochemical evidence that CFTR possesses intrinsic ATPase activity is lacking, In this study, we repo rt the first measurements of the rate of ATP hydrolysis by purified, r econstituted CFTR. The mutation CFTRG551D resides within a motif conse rved in many nucleotidases and is known to cause severe human disease. Following reconstitution the mutant protein exhibited both defective ATP hydrolysis and channel gating, providing direct evidence that CFTR utilizes ATP to gate its channel activity.