Structure of the ABC Transporter MsbA in Complex with ADP·Vanadate and Lipopolysaccharide
Christopher L. Reyes and
Geoffrey Chang*
Select members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family couple ATP binding and hydrolysis to substrate efflux and confer multidrug resistance. We have determined the x-ray structure of MsbA in complex with magnesium, adenosine diphosphate, and inorganic vanadate (Mg·ADP·Vi) and the rough-chemotype lipopolysaccharide, Ra LPS. The structure supports a model involving a rigid-body torque of the two transmembrane domains during ATP hydrolysis and suggests a mechanism by which the nucleotide-binding domain communicates with the transmembrane domain. We propose a lipid "flip-flop" mechanism in which the sugar groups are sequestered in the chamber while the hydrophobic tails are dragged through the lipid bilayer.
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road CB105, La Jolla, CA 92137, USA.
* To whom correspondence should be addressed. E-mail: gchang{at}scripps.edu
