CFTR is a member of the larger, ATP-Binding Cassette (ABC-) transporter family of proteins. This family is highly conserved evolutionarily and utilizes ATP binding and hydrolysis to facilitate solute movement in biological systems. The majority of ABC-transporters are transmembrane proteins and move impermeable substrates across the membrane.
A prototypical ABC-transporter exporter is shown as a cartoon on the left. The transmembrane domains (TMDs) cross the biological membrane (shown as dashed lines) and faciltiate solute movement. The TMDs are connected to the intracellular loops or domains (ICLs or ICDs) that link TMD movement to the nucleotide binding domains (NBDs), The NBDs bind and hydrolyze ATP to provide energy for solute transport. The core ABC-transporter is composed of two TMDs/ICLs and two NBDs, colored magenta and green. Additional transmembrane and soluble domains are found in multiple human ABC proteins, including the R-region of CFTR, which connects the first TMD and NBD (magenta) to the second (green). While most ABC- proteins funcation as active transporters, CFTR has evolved to utilize phosphorylation of the R-region and ATP-binding to its NBDs to regulate channel function, allowing chloride to move along its electro-chemical gradient.