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Prof. Dong Haohao’s team of SKLB reveals molecular mechanism of Gram-negative bacteria in Nature Structural & Molecular Biology

Recently, the research team led by Prof. Haohao Dong from the State Key Laboratory of Biotherapy of West China Hospital published a research paper entitled “Structural Insights into Outer Membrane Asymmetry Maintenance in Gram-negative Bacteria by MlaFEDB” in Nature Structural & Molecular Biology (IF: 12.109). This work analyzed the structure and function of the protein machine MlaFEDB and revealed the molecular mechanism of Gram-negative bacteria maintaining outer membrane asymmetry.

This study revealed four high-resolution cryo-electron microscopy structures of MlaFEDB, a protein-machine complex used by multidrug-resistant bacteria-Gram-negative bacteria to transport phospholipids to maintain the asymmetric structure of the outer membrane. The structures show substrate phospholipid-bound, AMP-PNP or ADP-bound conformations. Through structure analysis, in vivo cellular functional assays and in vitro fluorescence resonance energy transfer (FRET) phospholipid transport experiments, the functional residues of the protein machine and its efficient transport mechanism are comprehensively described.

Drug resistance of bacterial infection is one of the greatest challenges in the medical field. Gram-negative bacteria (Pseudomonas aeruginosa, enterobacter and acinetobacter baumannii) are clinically common pathogenic bacteria with drug resistance. This research has shed light for the research and development of new drugs to resist superbug infection, which is therapeutically significant.

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