This study reveals the cryo-electron microscopy structure of the core bacterial division complex FtsWIQLB and through functional analysis, identifies the key functional sites of FtsW, initially unveiling the mechanism of its binding and transport with the substrate Lipid II.

This study captures for the first time the multiple intermediate conformations of BAM and the substrate β-barrel protein EspP during the folding and integration process in the outer membrane, and reveals the whole process of the assembly, closure and release of the substrate OMP through in vivo and ex vivo functional analyses and all-atom molecular dynamics simulations, which will provide an important scientific basis for the research and development of novel antimicrobial drugs targeting this.

In this study, LolCDE (apo), a protein machine used by multidrug-resistant bacteria-gram-negative bacteria to transport the lipoprotein components of the outer membrane, and six high-resolution cryo-EM structures combined with substrate lipoprotein, ADP, ATP isomeric inhibitor AMP-PNP and periplasmic protein LolA, were analyzed, demonstrating four intermediate conformations in their transport functions.

This study revealed four high-resolution cryo-electron microscopic structures of MlaFEDB in an apo state and bound to phospholipid, ADP or AMP-PNP, which transport the phospholipids of the outer membrane to maintain the asymmetric structure of the outer membrane. The study also provided mechanistic insights into the Mla pathway by in vitro transport assays and in vivo membrane permeability assays combined with mutagenesis, which could aid antimicrobial drug development.

This study reveals the high-resolution cryo-EM structure of the protein machine complex LptB2FGC used by multidrug-resistant bacteria-gram-negative bacteria to transport outer membrane lipopolysaccharides, bound to its substrate lipopolysaccharide or AMP-PNP. Through the analysis of structure and the study of the function in the cell, the important functional sites of the protein machine and its high-efficiency transport mechanism are revealed.