A functionally rotating mechanism revealed in crystal structures of the multidrug transporter, AcrB, with bound substrates

Dept.Cell Membrane Biology, Inst. Scientific and Industrial Research, Osaka University
â—‹Satoshi Murakami

AcrB is a major multidrug efflux transporter in Escherichia coli cooperating with an outer membrane channel TolC and a membrane fusion protein AcrA. Here, we describe the new asymmetric crystal structure of AcrB in complex with its substrates. The AcrB-drug complex consists of three protomers, each of which represents one functional state of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers in its voluminous aromatic binding pocket in a multi-site binding mode. The structure clearly revealed that drugs are exported by a three-step functionally rotating ordered binding change mechanism.