(A) The resting state of the apo pump with TolC in closed-state and the AcrB trimer in LLL conformation. (B) The apo pump switches to a transport-state in the presence of transport substrate (s), opening the TolC channel (right arrow). In the transport-state, AcrB cycles through three, structurally distinct states (L, T and O), two of which are shown in the left panel (T and O). Cycling is obligatory for unidirectional transport, driven by coupling with transmembrane proton conduction through the TM domain (red arrow). In the absence of substrate, the pump reverts to the resting state and closes the TolC channel (left arrow). The views are cross-sections through the cell envelope, with only two protomers shown for each of the pump components. The inset cartoons on the left in (A) and the right in (B) show views down the molecular axis of the AcrB trimer, indicating the states with the configuration inferred from the cryoEM reconstructions. The model predicts a contraction along the long axis of the pump with the switch from apo- to transport-states.