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. Author manuscript; available in PMC: 2023 Jun 21.
Published in final edited form as: Annu Rev Biochem. 2022 Mar 23;91:705–729. doi: 10.1146/annurev-biochem-040320-105145

Figure 6.

Figure 6.

Mechanism of lipid II flipping by MurJ. Lipid II enters the central cavity through a lateral portal. The Arg24/Asp25/Arg255 triad in the cavity binds the diphosphate moiety of lipid II, while the undecaprenyl tail fits into the hydrophobic groove formed by TMs 13 and 14. Lipid II is occluded from the cytosol by the Glu57-Arg352 thin gate, poised for outward transition. Upon sodium binding to the C-lobe, MurJ transits to the outward-facing state, disengaging Arg255 from Arg24 and Asp25. Because the outward-facing cleft is too narrow to accommodate the lipid II headgroup, lipid II is released. Chloride binding reassociates the Arg24/Asp25/Arg255 triad, resetting MurJ to an inward-facing apo state where the portal is closed. Membrane potential might also facilitate this inward reset. Release of sodium and chloride ions into the cytosol mediates reopening of the portal, completing the transport cycle. The net reaction is the export of lipid II, uptake of one sodium ion, and uptake of one chloride ion.

Abbreviation: TM, transmembrane helix.