Abstract
In Escherichia coli, an important step in the divisome assembly pathway is the recruitment of the essential cell wall synthase complex FtsWI to the division site through interactions with the regulatory FtsQLB complex. Here, we investigate a key aspect of this recruitment by characterizing the structural organization of the FtsL-FtsW interaction. Mutations in the cytoplasmic and transmembrane regions of the two proteins result in cell division defects and loss of FtsW localization to division sites. We use these in vivo results to help validate the predicted interfaces from an AlphaFold2 model for the entire FtsQLBWI complex. Given the consistency between the predicted FtsQLBWI model and our current understanding of the structure and function of the complex, we further remodeled it, seeking insight into the potential structural transitions that may lead to activation of the FtsWI complex and PG synthesis. The model suggests that FtsLB serves as a support for FtsI, placing its periplasmic domain in an extended and possibly active conformation but it is also compatible with a proposed compact and possibly inactive conformation. Additionally, we reconfigure the model into an Fts[QLBWI]2 diprotomeric state, which suggests that FtsLB may act as a central hub during assembly of the PG synthesis machinery. Finally, we propose a possible role for FtsQ in activation of this machinery, potentially by acting as a gatekeeper for the interaction between the FtsL AWI region and FtsI. We propose that this gatekeeping function depends on a hinge next to the FtsLB CCD region, which has implications for the mechanisms behind the FtsLB off/on transition that is central to cell division regulation.
Competing Interest Statement
The authors have declared no competing interest.
