fig7

Figure 7. Unidirectional transport cycle in ABC exporters is driven by weak dipolar interactions between the allocrite and the transporter. (1) With two ATPs bound to the NBDs, the TMDs are in the outward closed resting state. The amphiphilic allocrite with HBAs in the polar part (blue) is attracted to the transporter via weak dipolar interactions. The polar groups are then drawn towards the center of the membrane (ε_m ≈ 2). (2) Hydrolysis of ATP and release of inorganic phosphate (P_i) lead to an asymmetric occupation state of the NBDs, which initiates the opening of the TMDs. (3) The TMDs adopt an outward open conformation, which allows influx of water molecules. The allocrite flops (i.e., it turns around to expose its polar part towards the aqueous phase). The hydrogen bonds between the allocrite and the transporter are dissolved. The binding of ATP to the empty NBS restores the symmetric occupancy state and favors the outward closed conformation. The allocrites on the extracellular side of the cavity between the TMDs are squeezed out to the membrane (see also Ref.^[33]).