Figure 4.

MsbA provides the crucial checkpoint by preferably selecting LPS with hexa-acylated lipid A. (a) MsbA has higher selectivity for hexa-acylated lipid A shown with a bold arrow. Selectivity for lipid IV_A or tetraacylated lipid A is highly reduced, depicted as dashed and thinner arrows. (b) Single amino acid substitutions mapping to the lipid A-binding domain or in the LPS exit groove of MsbA that allows the translocation of tetra-acylated Δ(waaA) or penta-acylated lipid A in Δ(clsA lpxM) translocation due to relaxation in hydrocarbon ruler properties. (c) Absence of cardiolipin is lethal when E. coli synthesizes underacylated LPS, which can be overcome by mutations in the msbA gene. Bold arrows indicate higher selectivity for hexa-acylated as compared to thinner or dashed arrows for tetra-acylated species. Inset shows the presence of cardiolipin.