Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide.
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.
Reyes
Christopher L
CL
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road CB105, La Jolla, CA 92137, USA.
Chang
Geoffrey
G
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000737:chemistry; D019281:Dimerization; D005583:Fourier Analysis; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers; D008070:Lipopolysaccharides / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D019897:Periplasm / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000737:chemistry*; D013379:Substrate Specificity; D014638:Vanadates / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D008051:Lipid Bilayers; D008070:Lipopolysaccharides; C079726:MsbA protein, Bacteria; D014638:Vanadates; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D008274:Magnesium