Structure and mechanism of drug efflux machinery in Gram negative bacteria.
In Gram-negative bacteria, multi-component machines that span the inner and outer membranes actively extrude drugs and other toxic small compounds. Many of these machines are assembled principally from three different types of components: i) an outer membrane protein that acts as a channel and opens from a sealed resting state during the transport process, ii) an inner membrane protein that transduces proton electrochemical energy into vectorial displacement of the transported compounds, and iii) a bridging, periplasmic component that links the inner and outer membrane proteins. The pumps may assemble transiently, and the association of components is favoured by engaged substrate and the trans-membrane electrochemical potential. We describe recent structural and functional studies on the individual pump components and discuss models that explain how they associate in the dynamic, active assembly. Based on the available data, we suggest that the assembly of these multi-drug efflux pumps is accompanied by induced fit of the outer membrane component driven mainly by accommodation of the periplasmic component.
Pietras
Zbigniew
Z
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
Bavro
Vassiliy N
VN
Furnham
Nicholas
N
Pellegrini-Calace
Marialuisa
M
Milner-White
E James
EJ
Luisi
Ben F
BF
D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism* / Q000502:physiology; D001692:Biological Transport; D024881:Drug Resistance, Bacterial; D004563:Electrochemistry; D006090:Gram-Negative Bacteria / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D011487:Protein Conformation
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins