Figure 5.

FtsI pedestal domain interaction with FtsW ECL4. FtsI (cyan) and FtsW (yellow) interact in the periplasm leading to the activation of FtsW. The membrane proximal part of the FtsI pedestal domain interacts with ECL4 of FtsW (orange). Activating (green) and suppressing (red) residues can be found in this region, and likely lead to stabilization of the active residue FtsW^D297 in the active site. The proximal part of the pedestal domain contains multiple residues divided over an α-helix and β-sheet that activate FtsW. These include residues G57, S61 and L62 located on α2, and residue R210 on β1. Residue K211, located adjacent to R210, inhibits FtsW activation, likely through an interaction with Q65. The pedestal domain interacts mostly with the FtsW region around M269, which activates GTase activity. A cluster of residues at the end of the pedestal domain is important for the stability of this domain and appears to be involved in the regulation of the FtsI-mediated activation of FtsW. Residue R167, proposed to interact with E193, stabilizes the domain and thus inhibits FtsW activation, though it may also affect the activity of the FtsI TPase domain.