Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation

J Mol Biol. 2003 Jul 4;330(2):419-30. doi: 10.1016/s0022-2836(03)00587-4.


The spread of multidrug resistance (MDR) is a world health crisis that presents a significant challenge to the treatment of cancer and infection. MDR can be caused by a group of ABC (MDR-ABC) transporters that move hydrophobic drug molecules and lipids across the cell membrane. To gain insight into the conformational changes these transporters undergo when flipping hydrophobic substrates across the lipid bilayer, we have determined the structure of the lipid flippase MsbA from Vibrio cholera (VC-MsbA) to 3.8A. Structural comparison of VC-MsbA to MsbA from Escherichia coli reveals that the transporters share a structurally conserved core of transmembrane alpha-helices, but differ in the relative orientations of their nucleotide-binding domains (NBD). The transmembrane domain of VC-MsbA is captured in a closed conformation and the structure supports a "power stroke" model of transporter dynamics where opposing NBDs associate upon ATP binding. The separation of the alpha and beta domains of the NBD suggests the possibility that their association could make them competent to bind ATP and gives further insight into the structural basis for catalytic regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Resistance, Multiple, Bacterial
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Vibrio cholerae / chemistry*
  • Vibrio cholerae / genetics


  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Escherichia coli Proteins
  • MsbA protein, Bacteria
  • Recombinant Proteins

Associated data

  • PDB/1PF4