Practice question

CFTR ABCC7 stands as atypical member of ABC superfamily because evolution transformed an active exporter scaffold into ATP-gated ion channel. Typical ABC exporters use ATP binding and hydrolysis to drive large TMD movements translocating substrate uphill. In CFTR, transmembrane domains create chloride-selective pore allowing passive flow down electrochemical gradient when open, while nucleotide-binding domains still bind ATP and regulate gating rather than transport solute stoichiometrically. Two ATP sites: NBD1 non-canonical hydrolyzes slowly, NBD2 drives channel closure upon hydrolysis. Additionally R domain phosphorylation by protein kinase A is required to permit NBD dimerization and opening. Thus transport is not solute-coupled uphill pumping but gated diffusion of Cl- and HCO3-, regulating airway surface liquid volume. This unique adaptation explains why potentiators like ivacaftor increase open probability and correctors assist folding, strategies distinct from inhibitors targeting classical ABC efflux pumps that expel hydrophobic drugs. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.