Proc. Natl. Acad. Sci. USA, published online 17 October 2011, doi:10.1073/pnas.1108323108

Proc. Natl. Acad. Sci. USA, published online 17 October 2011, doi:10.1073/pnas.1107780108

The ABC transporter–like FtsEX complex is a known component of the cell division apparatus, but its specific function has been unclear. During division, peptidoglycan remodeling is required to separate the two daughter cells: in Escherichia coli, EnvC activates the appropriate peptidoglycan hydrolases, but the regulatory mechanisms controlling EnvC and thus limiting undesired hydrolysis are unknown. In Streptococcus pneumoniae, PcsB contains hydrolase motifs, and its depletion is associated with defects in cell growth and separation, but biochemical assays have been unable to detect enzyme activity. Yang et al. and Sham et al. now unify these observations and provide a link between major cell division processes by demonstrating a physical and functional connection between the FtsEX complex and EnvC or PcsB. The two groups used a combination of deletion strains, subcellular fractionation and localization experiments, chemical crosslinking, and mutant constructs to show that the interaction involves an extracellular loop on FtsEX and the coiled-coil domains of EnvC or PcsB. Additionally, the interaction itself dictates both localization and activation of EnvC or PcsB, whereas activation, but not localization, requires ATP hydrolysis by FtsEX for EnvC and probably for PcsB. These results lead to a model in which conformational changes in FtsEX in response to ATP hydrolysis propagate to structural changes activating EnvC or PcsB, though the nature of these rearrangements requires further study.