Visualizing conformation transitions of the Lipid II flippase MurJ

Alvin C. Y. Kuk, Aili Hao, Ziqiang Guan and Seok-Yong Lee ()
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Alvin C. Y. Kuk: Duke University Medical Center
Aili Hao: Duke University Medical Center
Ziqiang Guan: Duke University Medical Center
Seok-Yong Lee: Duke University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract The biosynthesis of many polysaccharides, including bacterial peptidoglycan and eukaryotic N-linked glycans, requires transport of lipid-linked oligosaccharide (LLO) precursors across the membrane by specialized flippases. MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, and a target of recently discovered antibacterials. However, the flipping mechanism of LLOs including Lipid II remains poorly understood due to a dearth of structural information. Here we report crystal structures of MurJ captured in inward-closed, inward-open, inward-occluded and outward-facing conformations. Together with mutagenesis studies, we elucidate the conformational transitions in MurJ that mediate lipid flipping, identify the key ion for function, and provide a framework for the development of inhibitors.

Date: 2019
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DOI: 10.1038/s41467-019-09658-0

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