W0376

Structures of Multidrug Resistance ABC Transporter Homologs. Geoffrey Chang, Molecular Biology, The Scripps Research Inst., 10550 N. Torrey Pines, La Jolla, CA 92037 USA.

Multidrug resistance (MDR) presents a major challenge to the treatment of disease and the development of novel therapeutics. The x-ray structures of the multidrug resistance ABC (MDR-ABC) transporter homolog MsbA sheds light on the molecular structural basis of lipid/drug transport. MsbA is organized as a dimer with each subunit containing six transmembrane α-helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber in the cell membrane suggests a general mechanism for the translocation of hydrophobic substrate by MsbA and, by sequence homology, to other MDR-ABC transporters. The structures of MsbA can serve as a model for ABC transporters that export substrate and confer MDR to cancer cells and infectious microorganisms.