Schematic representation of the redox-driven Na + translocation mechanism. i : Fd transfers an electron via a chain of FeS cluster in RnfB to the terminal B8 cluster. ii : Reduction of B8 induces a conformational change in the B8-domain, which approaches RnfA/E on the cytosolic side. The conformational changes result in a shorter distance between B8 and AE1, enabling the electron transfer. iii : Reduction of AE1 increases the Na + binding affinity in RnfA/E that leads to Na + uptake from the cytosol. iv : After Na + binding next to AE1, RnfA/E undergoes an inward/outward transition that, in turn, moves RnfG closer to RnfA/E. v : Electron transfer from AE1 to FMN G lowers the binding affinity for Na + , and results in the Na + release to the extracellular side. The electron is transferred from FMN G to the RnfC FeS via the flavins on RnfD, in a process that couples to the relaxation of RnfA/E to its inward-open state. The reduction of C2 increases the affinity of RnfC for NAD + , which binds next to the FMN C . vi-ix : similar to previous steps, another electron transfer from Fd couples to the translocation of a second Na + . x : Two-electron reduction yields FMNH - , which reduces NAD + to NADH via a hydride transfer, initiating a new pumping cycle.
