Figure 7.

Model for the mechanism of action of Lpo proteins. A. The docking domain of the PBP interacts with its cognate Lpo, and undergoes a conformational change that repositions its TPase domain so that peptide crosslinking is stimulated. Glycan chains are sandwiched between the IM and OM, and are composed of N-acetylglucosamine (G) and N-acetylmuramic acid (M) depicted as hexagons. Attached to the M sugar are short peptides (balls) that crosslink the glycan strands. The 3-domain PBP is anchored to the IM [blue:TPase; green:GTase; orange: docking domain (UB2H/ODD)], and the Lpo protein (cylinder) is anchored to the OM. B. PBP1A-LpoA & PBP1B-LpoB are primarily responsible respectively for sidewall and septal PG synthesis. Cytoskeletal elements and the large elongasome/divisome complexes assembled around them recruit PBP1A at the lateral wall of elongating cells and PBP1B at septa of dividing cells. Here, IM components of these complexes are depicted as colored ovals, and periplasmic/OM components, including PG hydrolases and other PBPs, are omitted for clarity. LpoA and LpoB mirror the localization of their cognate PBP. Lpo proteins localize independently of their cognate PBP possibly via interaction with newly synthesized PG and/or via yet unidentified interactions to elongasome/divisome members. Despite their localization preferences, each PBP-Lpo complex can substitute for the loss of the other, which is reflected by the presence of both as foci at the lateral wall of cells and also at midcell of dividing cells. The docking domains for PBP1A (ODD) and PB1B (UB2H) are depicted here in orange and gold respectively.