Abstract
Membrane transport in cells is a fundamental biological process that is mediated by various channels, pumps and transporter proteins. AcrB is a major multidrug efflux transporter in gram-negative bacteria, which confer multidrug resistance. AcrB transports a wide variety of drugs or toxic compounds directly out of the cells driven by proton motive force. Now we solve the crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of asymmetric three protomers, each of which has different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures show that drugs are presumably exported by a three-step functionally rotating mechanism in which drugs undergo ordered binding change.
