AcrA is a dynamic protein which ensures a sealed connecting pore between the AcrB transporter and the outer membrane factor TolC. Importantly, AcrA transmits conformational motions during substrate recognition and translocation by AcrB for the gating of TolC to enable drug export from the periplasm to the outside of the gram-negative bacterial wall. The periplasmic space has a pH like that of the external medium. When that external environment becomes more acidic, for example during enteric infection and colonization, then an acidified periplasmic space will occur and His285 becomes protonated. His285 is critical for modulating the hydrogen bonding network within AcrA. In a low Mg2+environment AcrA undergoes a global increase in conformational plasticity which could prevent proper multidrug efflux pump function or pore concealment of its substrates. Whereas, within a Mg2+-rich environment, at acidic pH, regions of the barrel domain are stabilized and exhibit structural reorganization, likely to ensure proper function within increased acidity. PG, peptidoglycan layer.
