Catalytic cycle of EtfABCX. The complex is depicted in its resting one-electron reduced state in which the ET-FAD is in the ASQ state. Conformational changes (indicated by asterisks) are required to bring the complex into a bifurcation-ready state (ET-FAD and BF-FAD within 14 Å), designated states A and A′. We propose that this involves the binding of both NADH and Fd. The A, A′, B, C, and D states are defined in the legend to Fig. 3. For clarity, the EtfC–EtfX subcomplex is depicted only when there is a change in redox states compared with the previous step of the cycle.