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This article has been retracted

Science 7 September 2001:
Vol. 293. no. 5536, pp. 1793 - 1800
DOI: 10.1126/science.293.5536.1793
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Research Articles

Structure of MsbA from E. coli: A Homolog of the Multidrug Resistance ATP Binding Cassette (ABC) Transporters

Geoffrey Chang,* Christopher B. Roth

Multidrug resistance (MDR) is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance (MDR-ABC transporters) translocate hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. To better elucidate the structural basis for the "flip-flop" mechanism of substrate movement across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallography to a resolution of 4.5 angstroms. MsbA is organized as a homodimer with each subunit containing six transmembrane alpha -helices and a nucleotide-binding domain. The asymmetric distribution of charged residues lining a central chamber suggests a general mechanism for the translocation of substrate by MsbA and other MDR-ABC transporters. The structure of MsbA can serve as a model for the MDR-ABC transporters that confer multidrug resistance to cancer cells and infectious microorganisms.

Department of Molecular Biology, MB-9, The Scripps Research Institute, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: gchang{at}scripps.edu

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HDL Apolipoproteins and ABCA1: Partners in the Removal of Excess Cellular Cholesterol.
J. F. Oram (2003)
Arterioscler Thromb Vasc Biol 23, 720-727
   Abstract »    Full Text »    PDF »
Three-dimensional Reconstruction of the Saccharomyces cerevisiae Multidrug Resistance Protein Pdr5p.
A. Ferreira-Pereira, S. Marco, A. Decottignies, J. Nader, A. Goffeau, and J.-L. Rigaud (2003)
J. Biol. Chem. 278, 11995-11999
   Abstract »    Full Text »    PDF »
Origin of the 2-Amino-2-deoxy-gluconate Unit in Rhizobium leguminosarum Lipid A. EXPRESSION CLONING OF THE OUTER MEMBRANE OXIDASE LpxQ.
N. L. S. Que-Gewirth, M. J. Karbarz, S. R. Kalb, R. J. Cotter, and C. R. H. Raetz (2003)
J. Biol. Chem. 278, 12120-12129
   Abstract »    Full Text »    PDF »
The ATP-Binding Cassette Transporters: Structure, Function, and Gene Family Comparison between Rice and Arabidopsis.
M. Jasinski, E. Ducos, E. Martinoia, and M. Boutry (2003)
Plant Physiology 131, 1169-1177
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Three-dimensional Structures of the Mammalian Multidrug Resistance P-glycoprotein Demonstrate Major Conformational Changes in the Transmembrane Domains upon Nucleotide Binding.
M. F. Rosenberg, A. B. Kamis, R. Callaghan, C. F. Higgins, and R. C. Ford (2003)
J. Biol. Chem. 278, 8294-8299
   Abstract »    Full Text »    PDF »
Modulation of the Trafficking Efficiency and Functional Properties of ATP-sensitive Potassium Channels through a Single Amino Acid in the Sulfonylurea Receptor.
E. A. Cartier, S. Shen, and S.-L. Shyng (2003)
J. Biol. Chem. 278, 7081-7090
   Abstract »    Full Text »    PDF »
Intermediate Structural States Involved in MRP1-mediated Drug Transport. ROLE OF GLUTATHIONE.
L. Manciu, X.-B. Chang, F. Buyse, Y.-X. Hou, A. Gustot, J. R. Riordan, and J. M. Ruysschaert (2003)
J. Biol. Chem. 278, 3347-3356
   Abstract »    Full Text »    PDF »
On the Mechanism of MgATP-dependent Gating of CFTR Cl- Channels.
P. Vergani, A. C. Nairn, and D. C. Gadsby (2002)
J. Gen. Physiol. 121, 17-36
   Abstract »    Full Text »    PDF »
Regulation of Bacterial Drug Export Systems.
S. Grkovic, M. H. Brown, and R. A. Skurray (2002)
Microbiol. Mol. Biol. Rev. 66, 671-701
   Abstract »    Full Text »    PDF »
SUR-dependent Modulation of KATP Channels by an N-terminal KIR6.2 Peptide. DEFINING INTERSUBUNIT GATING INTERACTIONS.
A. P. Babenko and J. Bryan (2002)
J. Biol. Chem. 277, 43997-44004
   Abstract »    Full Text »    PDF »
The "LSGGQ" Motif in Each Nucleotide-binding Domain of Human P-glycoprotein Is Adjacent to the Opposing Walker A Sequence.
T. W. Loo, M. C. Bartlett, and D. M. Clarke (2002)
J. Biol. Chem. 277, 41303-41306
   Abstract »    Full Text »    PDF »
Structural Biology of Bacterial Multidrug Resistance Gene Regulators.
M. H. Godsey, E. E. Zheleznova Heldwein, and R. G. Brennan (2002)
J. Biol. Chem. 277, 40169-40172
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Projection Structure of P-glycoprotein by Electron Microscopy. EVIDENCE FOR A CLOSED CONFORMATION OF THE NUCLEOTIDE BINDING DOMAINS.
J.-Y. Lee, I. L. Urbatsch, A. E. Senior, and S. Wilkens (2002)
J. Biol. Chem. 277, 40125-40131
   Abstract »    Full Text »    PDF »


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