ABCtransporters

ABC transporters, or ATP-binding cassette transporters, are a large and diverse superfamily of membrane proteins that use the energy of ATP hydrolysis to move substrates across cellular membranes. They are found in bacteria, archaea, and eukaryotes, and participate in nutrient uptake, lipid transport, toxin and drug efflux, ion transport, and more. In humans they influence drug disposition, absorption, and excretion, as well as physiological processes such as cholesterol and lipid transport.

Structural and mechanistic overview: most ABC transporters contain two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP and two transmembrane domains (TMDs) that form the substrate pathway. In many exporters, a single polypeptide includes both NBDs and TMDs (full transporters); in some systems, half-transporters with one NBD and one TMD dimerize to function. The transport cycle involves ATP binding, conformational changes that switch the substrate-binding site from one side of the membrane to the other (alternating access), substrate translocation, and ATP hydrolysis to reset the transporter.

Diversity and roles: ABC transporters are categorized into subfamilies (for example, ABC A through ABC G). In humans, P-glycoprotein (ABCB1) extrudes a wide range of drugs and xenobiotics; CFTR (ABCC7) functions as an ion channel rather than a conventional transporter; ABCA transporters are implicated in lipid transport; bacterial ABC exporters contribute to antibiotic resistance and toxin efflux. Bacterial import systems also exist but operate with different subunit arrangements.

Clinical and research relevance: ABC transporters influence pharmacokinetics, drug interactions, and resistance. Overexpression of efflux pumps like ABCB1 is associated with multidrug resistance in cancer; CFTR mutations cause cystic fibrosis. Ongoing research seeks inhibitor strategies to overcome resistance, CFTR modulators for therapy, and ways to harness transporters for targeted drug delivery.