Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa.
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.
Department of Biochemistry, University of Zurich, Switzerland.
Gaby
G
Sennhauser
Magdalena A
MA
Bukowska
Christophe
C
Briand
Markus G
MG
Grütter
D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D024901:Drug Resistance, Multiple, Bacterial; D029968:Escherichia coli Proteins / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000737:chemistry*; D016415:Sequence Alignment; D040681:Structural Homology, Protein
D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083496:AcrB protein, E coli; C118597:MexB protein, Pseudomonas aeruginosa