Fig. 4: Bilayer-assisted chemo-mechanical coupling in the transport cycle of group II ECF transporters.

Schematic representation of the different states in the transport cycle of group II ECF transporters with exchangeable S-components. State 1: The inward-facing apo conformation of the ECF transporter complex, from which substrate has been released into the cell. The S-component locally deforms the membrane to keep the positively charged base solvent exposed. The docking surface on the EcfT subunit for the S-component displays concave-shaped coupling helices. State 2: Upon binding of Mg-ATP, the ATPase dimer changes from an open to a closed configuration. This leads to a propagated change in the coupling helices that move into the membrane to adopt a convex shape (spring loaded), and to a reshaping of the local bilayer. Both features guide the reorientation to an outward-facing state and the expulsion of the S-component from the complex into the lipid bilayer. The EcfT transmembrane domain takes the space left by the expelled S-component into the membrane. State 3: Upon the hydrolysis of ATP and release of ADP and P_i, the coupling helices return to their original concave shape with the EcfT transmembrane domain moving away from the docking site for the S-component, which restores the interaction surface (spring release) and creates space for the binding of a new S-component, for the same or a different substrate (competition). State 4: The solitary ECF module assumes a tilted conformation to locally thin and bend the membrane, guiding a substrate-bound S-component to topple within the membrane to form a stable complex with the ECF module.