Visualizing conformation transitions of the Lipid II flippase MurJ

Kuk, Alvin C. Y.; Hao, Aili; Guan, Ziqiang; Lee, Seok-Yong

doi:10.1038/s41467-019-09658-0

Title: Visualizing conformation transitions of the Lipid II flippase MurJ

Journal Article · Mon Apr 15 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-09658-0· OSTI ID:1513008

^[1]; Hao, Aili ^[1]; Guan, Ziqiang ^[1];

^[1]

Duke Univ. Medical Center, Durham, NC (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Inst. of Health

Grant/Contract Number:: R01GM120594; GM124165; RR029205; OD021527

OSTI ID:: 1513008

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 36 works

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