Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
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 tosubstrate efflux and confer multidrug resistance. We have determinedthe x-ray structure of MsbA in complex with magnesium, adenosinediphosphate, and inorganic vanadate (Mg·ADP·Vi)and the rough-chemotype lipopolysaccharide, Ra LPS. The structuresupports a model involving a rigid-body torque of the two transmembranedomains during ATP hydrolysis and suggests a mechanism by whichthe nucleotide-binding domain communicates with the transmembranedomain. We propose a lipid "flip-flop" mechanism in which thesugar groups are sequestered in the chamber while the hydrophobictails 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
Amy L. Davidson and Jue Chen (13 May 2005) Science308 (5724), 963.
[DOI: 10.1126/science.1113414] |Summary »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Flexibility in the ABC transporter MsbA: Alternating access with a twist.
A. Ward, C. L. Reyes, J. Yu, C. B. Roth, and G. Chang (2007)
PNAS
104, 19005-19010
|Abstract »|Full Text »|PDF »
In vitro susceptibility of Staphylococcus aureus to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry.
K. Mukhopadhyay, W. Whitmire, Y. Q. Xiong, J. Molden, T. Jones, A. Peschel, P. Staubitz, J. Adler-Moore, P. J. McNamara, R. A. Proctor, et al. (2007)
Microbiology
153, 1187-1197
|Abstract »|Full Text »|PDF »
Structural and Functional Fingerprint of the Mitochondrial ATP-binding Cassette Transporter Mdl1 from Saccharomyces cerevisiae.
M. Hofacker, S. Gompf, A. Zutz, C. Presenti, W. Haase, C. van der Does, K. Model, and R. Tampe (2007)
J. Biol. Chem.
282, 3951-3961
|Abstract »|Full Text »|PDF »
Phospholipid Flippases.
D. L. Daleke (2007)
J. Biol. Chem.
282, 821-825
|Full Text »|PDF »
About a switch: how P-glycoprotein (ABCB1) harnesses the energy of ATP binding and hydrolysis to do mechanical work.
ATP Induces Conformational Changes of Periplasmic Loop Regions of the Maltose ATP-binding Cassette Transporter.
M. L. Daus, H. Landmesser, A. Schlosser, P. Muller, A. Herrmann, and E. Schneider (2006)
J. Biol. Chem.
281, 3856-3865
|Abstract »|Full Text »|PDF »
Functional Asymmetry of Nucleotide-binding Domains in ABCG5 and ABCG8.
D.-W. Zhang, G. A. Graf, R. D. Gerard, J. C. Cohen, and H. H. Hobbs (2006)
J. Biol. Chem.
281, 4507-4516
|Abstract »|Full Text »|PDF »
Functional Importance of Three Basic Residues Clustered at the Cytosolic Interface of Transmembrane Helix 15 in the Multidrug and Organic Anion Transporter MRP1 (ABCC1).
G. Conseil, R. G. Deeley, and S. P. C. Cole (2006)
J. Biol. Chem.
281, 43-50
|Abstract »|Full Text »|PDF »
The Block of CFTR by Scorpion Venom is State-Dependent.
M. D. Fuller, Z.-R. Zhang, G. Cui, and N. A. McCarty (2005)
Biophys. J.
89, 3960-3975
|Abstract »|Full Text »|PDF »
The Q-loop Disengages from the First Intracellular Loop during the Catalytic Cycle of the Multidrug ABC Transporter BmrA.
O. Dalmas, C. Orelle, A.-E. Foucher, C. Geourjon, S. Crouzy, A. Di Pietro, and J.-M. Jault (2005)
J. Biol. Chem.
280, 36857-36864
|Abstract »|Full Text »|PDF »
Use of an Efflux-Deficient Streptococcus pneumoniae Strain Panel To Identify ABC-Class Multidrug Transporters Involved in Intrinsic Resistance to Antimicrobial Agents.
G. T. Robertson, T. B. Doyle, and A. S. Lynch (2005)
Antimicrob. Agents Chemother.
49, 4781-4783
|Abstract »|Full Text »|PDF »
Drug-Lipid A Interactions on the Escherichia coli ABC Transporter MsbA.
B. Woebking, G. Reuter, R. A. Shilling, S. Velamakanni, S. Shahi, H. Venter, L. Balakrishnan, and H. W. van Veen (2005)
J. Bacteriol.
187, 6363-6369
|Abstract »|Full Text »|PDF »
The C-terminal Domain of the Nucleotide-binding Domain Protein Wzt Determines Substrate Specificity in the ATP-binding Cassette Transporter for the Lipopolysaccharide O-antigens in Escherichia coli Serotypes O8 and O9a.
L. Cuthbertson, J. Powers, and C. Whitfield (2005)
J. Biol. Chem.
280, 30310-30319
|Abstract »|Full Text »|PDF »
Structural Basis of Energy Transduction in the Transport Cycle of MsbA.