Figure 4.
Crystal structures of MurJTA in inward-open, inward-occluded, outward, and inward-closed states elucidate the conformational changes that mediate lipid II flipping. (a) The lateral membrane portal is opened in the inward-open conformation by the bending of TM1 out into the membrane and concomitant rearrangements in TM8 and the TM4–5 loop (orange), specifically those involving the Phe151 lever, allowing entry of the large lipid II headgroup into the cavity. Translucent outlines denote the other inward-facing conformations. (b) In the inward-occluded structure, Arg24 and Arg255 are brought into unusual proximity at the apex of the cavity, their electrostatic repulsion possibly stabilized by Asp25 and the anionic diphosphate moiety of lipid II (orange oval). TM1 is hidden in this panel for clarity. Translucent sticks denote these residues in the other inward-facing conformations. Arg255 is disengaged from this Arg24-Asp25-Arg255 triad in the outward-facing conformation. (c) Bending of TM2 and closing of the C-lobe forms a thin gate between Glu57 of the N-lobe and Arg352 of the C-lobe, possibly to occlude the lipid II headgroup from the cytosol. Translucent sticks denote these residues in the other inward-facing conformations.
Abbreviation: MurJTA, Thermosipho africanus MurJ; TM, transmembrane helix.