ATP Binding Cassette Transporters (ABC transporters) are a large family of membrane proteins found in both prokaryotes and eukaryotes, responsible for the energy-dependent transport of a wide variety of molecules across cellular membranes. They play a crucial role in maintaining cellular homeostasis by transporting essential nutrients, ions, metabolites, and lipids, as well as protecting cells against harmful substances and xenobiotics.
ABC transporters derive their name from their characteristic ability to bind and hydrolyze adenosine triphosphate (ATP), the energy currency of the cell. This ATP-driven transport process is responsible for the translocation of substrates against their concentration gradient, a mechanism known as active transport. By harnessing the energy from ATP hydrolysis, ABC transporters use conformational changes in their protein structure to facilitate substrate binding, translocation, and release.
These transporters consist of four domains: two cytoplasmic nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). The NBDs contain highly conserved ATP-binding motifs, while the TMDs form a translocation pathway across the lipid bilayer that accommodates various substrates. The binding and hydrolysis of ATP by the NBDs induce conformational changes in the TMDs, enabling the transport of substrates across the membrane.
ABC transporters exhibit a remarkable substrate spectrum, including ions, sugars, amino acids, peptides, lipids, and drugs. Their crucial role in the absorption, distribution, and elimination of drugs has made them key determinants of drug pharmacokinetics and drug resistance in various diseases, including cancer. Consequently, ABC transporters have emerged as important targets for the development of therapeutics and treatment strategies.
