Conformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism

The bacterial divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during division. Here, we present a model of the structure and dynamics of the core complex of the E. coli divisome, supported by a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. We focus on the septal cell wall synthase complex formed by FtsW and FtsI, and its regulators FtsQ, FtsL, FtsB, and FtsN. The results indicate extensive interactions in four regions in the periplasmic domains of the complex. FtsQ, FtsL, and FtsB support FtsI in an extended conformation, with the FtsI transpeptidase domain lifted away from the membrane through interactions among the C-terminal domains. FtsN binds between FtsI and FtsL in a region rich in residues with superfission (activating) and dominant negative (inhibitory) mutations. Mutagenesis experiments and simulations suggest that the essential domain of FtsN links FtsI and FtsL together, potentially modulating interactions between the anchor-loop of FtsI and the putative catalytic cavity of FtsW, thus suggesting a mechanism of how FtsN activates the cell wall synthesis activities of FtsW and FtsI. The divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during bacterial cell division. Here, the authors provide insights into the structure and dynamics of the divisome core complex using a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis.

Automated summary

In this study, the structure and dynamics of the E. coli divisome core complex were investigated using various techniques including structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis. The interactions and roles of proteins FtsW, FtsI, FtsQ, FtsL, FtsB, and FtsN in the complex were explored. The findings provide insights into the mechanism of cell wall synthesis activation by FtsN through modulating interactions between FtsI and FtsW.