Acell must selectively translocate molecules across its plasma membrane to maintain the chemical composition of its cytoplasm distinct from that of the surrounding milieu. The most intriguing, and, arguably, the most important membrane proteins for this purpose are the ABC (ATP-binding cassette) transporters. These proteins, found in all species, use the energy of ATP hydrolysis to translocate specific substrates across cellular membranes. The chemical nature of the substrates handled by ABC transporters is extremely diverse—from inorganic ions to sugars and large polypeptides—yet ABC transporters are highly conserved. Mutations in the genes encoding many of the 48 or so ABC transporters of human cells are associated with diseases such as cystic fibrosis, adrenoleukodystrophy, Tangier disease, and obstetric cholestasis. Overexpression of certain ABC transporters is the most frequent cause of resistance to cytotoxic agents including antibiotics, antifungals, herbicides, and anticancer drugs.

Despite years of work on both bacterial and mammalian ABC transporters, particularly the multidrug resistance transporter P-glycoprotein, it is still not clear exactly how these proteins work. Enter Chang and Roth (1) on page 1793 of this issue with the first high-resolution structure of a complete ABC transporter, the MsbA lipid A transporter of the bacterium Escherichia coli. Theirs is a remarkable achievement, given the difficulties inherent in working with