PROBING THE STRUCTURAL AND FUNCTIONAL DOMAINS OF THE CFTR CHLORIDE CHANNEL

The cystic fibrosis transmembrane conductance regulator (CFTR) forms a n anion-selective channel involved in epithelial chloride transport. R ecent studies have provided new insights into the structural determina nts of the channel's functional properties, such as anion selectivity, single-channel conductance, and gating. Using the scanning-cysteine-a ccessibility method we identified 7 residues in the M1 membrane-spanni ng segment and 11 residues in and flanking the M6 segment that are exp osed on the water-accessible surface of the protein; many of these res idues may line the ion-conducting pathway. The pattern of the accessib le residues suggests that these segments have a largely alpha-helical secondary structure with one face exposed in the channel lumen. Our re sults suggest that the residues at the cytoplasmic end of the M6 segme nt loop back into the channel, narrowing the lumen, and thereby formin g both the major resistance to ion movement and the charge-selectivity filter.