The ABC transporter structure and mechanism: perspectives on recent research

ATP-binding cassette (ABC) transporters are multidomain integral membrane proteins that utilise the energy of ATP hydrolysis to translocate solutes across cellular membranes in all phyla. ABC transporters form one of the largest of all protein families and are central to many important biomedical phenomena, including resistance of cancers and pathogenic microbes to drugs. Elucidation of the structure and mechanism of ABC transporters is essential to the rational design of agents to control their function. While a wealth of high-resolution structures of ABC proteins have been produced in recent years, many fundamental questions regarding the proteins mechanism remain unanswered. In this review, we examine the recent structural data concerning ABC transporters and related proteins in the light of other experimental and theoretical data, and discuss these data in relation to current ideas concerning the transporters molecular mechanism.Received 29 August 2003; received after revision 19 November 2003; accepted 28 November 2003