Membrane properties control the ATPase activity of the ABC transporter BmrA

Abstract

The structure and the function of membrane proteins can be affected by the lipid bilayer environment, yet its impact is often neglected in in vitro studies where proteins are typically analyzed in membrane mimetics, mostly liposomal systems. It has been observed that the activity of the bacterial ATP-binding cassette (ABC) transporter BmrA (Bacillus multidrug resistance ATP) differs when measured in detergent vs. a model membrane environment, indicating that the physico-chemical properties of the membrane environment crucially affect the protein's activity. We now performed a systematic analysis to elucidate the impact of individual lipid/membrane properties on the activity of BmrA and identified three parameters controlling the BmrA activity in lipid bilayers: (i) the hydrophobic thickness of the membrane, (ii) a negative surface charge, and (iii) the packing of lipids in the acyl-chain and head group regions. Our study provides valuable insights into how a specific lipid composition can influence the basal ATPase activity of BmrA and emphasizes that the lipid composition should be carefully selected in in vitro studies of membrane proteins.