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

Nat Commun. 2023 Jul 31;14(1):4585. doi: 10.1038/s41467-023-39921-4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Division
  • Cell Wall / metabolism
  • Escherichia coli Proteins* / metabolism
  • Escherichia coli* / metabolism
  • Membrane Proteins / metabolism


  • Escherichia coli Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • Bacterial Proteins