Multifaceted structures and mechanisms of ABC transport systems in health and disease

ATP-binding cassette (ABC) transporters are found in all domains of life and constitute one of the largest protein superfamilies. ABC transporters harness the energy of ATP binding and hydrolysis to shuttle a diverse range of substrates across cell membranes. While higher-resolution structures of ABC transporters have so far exclusively been obtained by X-ray crystallography, recent advances in single-particle cryogenic electron microscopy (cryo-EM) have provided a deluge of exciting new structures of medically relevant bacterial and human ABC proteins, including those of the cystic fibrosis transmembrane conductance regulator (CFTR), and of supramolecular assemblies involving ABC transporters, like the ATP-sensitive potassium (K_ATP) channel and the peptide-loading complex (PLC), which is crucially involved in the presentation of antigens in adaptive immunity.