Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa

J Mol Biol. 2009 May 29;389(1):134-45. doi: 10.1016/j.jmb.2009.04.001. Epub 2009 Apr 8.

Abstract

We report here the crystal structure of the Pseudomonas aeruginosa multidrug exporter MexB, an intensively studied member of the resistance-nodulation-cell division family of secondary active transporters, at 3.0 A. MexB forms an asymmetric homotrimer where each subunit adopts a different conformation representing three snapshots of the transport cycle similar to the recently determined structures of its close homologue AcrB from Escherichia coli, so far the sole structurally characterized member of the superfamily. As for AcrB, the conformations of two subunits can be clearly assigned to either the binding step or the extrusion step in the transport process. Unexpectedly, a remarkable conformational shift in the third subunit is observed in MexB, which has potential implications for the assembly of the tripartite MexAB-OprM drug efflux system. Furthermore, an n-dodecyl-d-maltoside molecule was found bound to the internal multidrug-binding cavity, which might indicate that MexB binds and transports detergent molecules as substrates. As the only missing piece of the puzzle in the MexAB-OprM system, the X-ray structure of MexB completes the molecular picture of the major pump mediating intrinsic and acquired multidrug resistance in P. aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Outer Membrane Proteins / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Resistance, Multiple, Bacterial*
  • Escherichia coli Proteins / chemistry
  • Membrane Transport Proteins / chemistry*
  • Molecular Sequence Data
  • Multidrug Resistance-Associated Proteins / chemistry
  • Protein Structure, Secondary
  • Pseudomonas aeruginosa / chemistry*
  • Sequence Alignment
  • Structural Homology, Protein

Substances

  • AcrB protein, E coli
  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Membrane Transport Proteins
  • MexB protein, Pseudomonas aeruginosa
  • Multidrug Resistance-Associated Proteins

Associated data

  • PDB/2V50