Figure 1: Schematic of a general ABC protein. The diagram is based on P-glycoprotein in its closed dimer conformation. The nucleotide-binding domains (NBDs) are the biological engines of ABCs and are located in the cytoplasm. The ATP at the dimer interface functions as the "molecular glue" in holding the dimer in its closed head-to-tail conformation. The transmembrane domains (TMDs) span the lipid bilayer and provide the translocation pathway. In normal ABC transporters, ligand transport entails conformational changes transmitted through TMDs to translocate the ligand across the membrane and subsequent lowering of affinity at the ligand-binding site releases the ligand on the other side of the membrane. CFTR on the other hand acts as a channel and the role of the TMDs is simply to form the pore for chloride ion transport. Nevertheless, all ABCs have the basic domain structure together with the highly conserved NBDs and this gives rise to the notion that perhaps there is a general mechanism, such as the ATP Switch model, that can be uniquely adapted for each ABC protein.