Research fellow Haohao Dong and his team at SCU State Key Laboratory of Biotherapy and Cancer Center have recently published in Nature Communications ( IF=11.878 ) a paper entitled “Cryo-EM structures of lipopolysaccharide transporter LptB2FGC in lipopolysaccharide or AMP-PNP-bound states reveal its transport mechanism”. The main work of this study is credited to Haohao Dong's team and Professor Xing Zhang, Director of theCenter of Cryo Electron Microscopy, Zhejiang University.The first authors include Dr. Xiaodi Tang, associate professor of SCU State Key Laboratory of Biotherapy and Cancer Center; Dr. Shenghai Chang ofCenter of Cryo Electron Microscopy, Zhejiang University; SCU doctoral student of Qinghua Luo and Zhengyu Zhang, a research fellow at Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University. Sichuan University State Key Laboratory of Biotherapy andCancer Center / National Clinical Research Center for Geriatrics is the first corresponding work unit.

“Antibiotic resistance of Gram-negative bacteria has become one of the greatest threats to global health.” ( Introduction of the research paper )

“The cryo-EM structure reveals a clear LPS density in the central cavity ( Fig. 1b ), showing all six acyl tails, glucosamine disaccharide phosphorylated at 1′ and 4′ positions, and the inner core oligosaccharide. The LPS molecule trapped is a natural substrate of sfLptB₂FG that was overexpressed in the E. coli C43 ( DE3 ) strain. The acyl tails of LPS are drooped and perpendicular to the IM plane in the upper cavity and the inner core positioned above in the periplasmic space (Fig. 1b–d). In the cavity, hydrophobic residues I25, F26, L62, L66, L70 and M303 of LptF and L26, I33, I66, F67, I313, F317 and Y320 of LptG interact with the LPS acyl tails via van der Waals interactions. Charged residues K34, K62, R133 and R136 of LptG and R33 of LptF form salt bonds with the 1′-phosphate group of LPS, while K40 of LptG and K317 of LptF form salt bonds with the 4′-phosphate group of LPS. D37 of LptG interacts with the glucosamine disaccharide of lipid A. K322, R263 and Q248 of LptF and K41 of LptG interact with the inner core oligosaccharide (Fig. 2a, b). Previously, we reported that mutants of the hydrophobic residues F26D and L62D of LptF in the cavity severely impaired cell viability.” ( Results of the paper )

This study is of great significance for the development of new drugs against superbacterial infections.

Article link: https://www.nature.com/articles/s41467-019-11977-1