Divisome core complex in bacterial cell division revealed by cryo-EM

Abstract

Cell division, or cytokinesis is a fundamental process of life and, in most bacteria, is driven by peptidoglycan synthesis at the septum1. It is catalysed by the divisome, a multi-protein complex with more than 20 components that spans the cell envelope in bacteria harbouring a cell wall2. Central to the divisome is the peptidoglycan-synthesising protein complex FtsWI, with the transglycosylase (TG) FtsW polymerising glycan strands from its substrate Lipid II3,4, and the transpeptidase (TP) FtsI crosslinking peptide stems, thus forming a covalent mesh between glycan strands5,6(Fig. 1a). Septal peptidoglycan synthesis occurs after activation of the divisome glycosyltransferase-transpeptidase pair FtsWI3, in particular through an interaction with the heterotrimer FtsQBL7.Here, we present the cryo-EM structure of the catalytic divisome core complex FtsWIQBL fromPseudomonas aeruginosaat 3.7 Å resolution. The structure reveals the intricate details of the periplasmic interfaces within FtsWIQBL, including the positioning of FtsI by the coiled coil of FtsBL, as well as a transmembrane domain containing FtsWIBL but not FtsQ. With our structure we are able to provide molecular mechanisms of a multitude of known mutations that interfere with divisome activation and regulation. Finally, we reveal a large conformational switch between presumably inactive and active states of the FtsWI core enzymes.Our work is foundational for further structural, biochemical and genetic studies elucidating the molecular mechanisms of bacterial cell division. Since the divisome peptidoglycan synthase is essential for cell division in most bacteria, and is absent in eukaryotic cells entirely, it is a key target of important antibiotics and antibiotic development8, and we suggest that our structure will help to accelerate these efforts.