CONFORMATIONAL STATES OF CFTR ASSOCIATED WITH CHANNEL GATING - THE ROLE OF ATP BINDING AND HYDROLYSIS

CFTR is a member of the traffic ATPase superfamily and a C1(-) ion cha nnel that appears to require ATP hydrolysis for gating. Analysis of si ngle CFTR C1(-) channels reconstituted into planar lipid bilayers reve aled the presence of two open conductance states that are connected to each other and to the closed state by an asymmetric cycle of gating e vents. We show here that the transition between the two open conductan ce states is directly coupled to ATP hydrolysis by one of the consensu s nucleotide-binding folds, designated NBF2. Moreover, the transition between the closed state and one of the open states is linked to the b inding of ATP. This analysis permits real-time visualization of confor mational changes associated with a single cycle of ATP hydrolysis by a single protein molecule and suggests a model describing a role for AT P in CFTR gating.