Visualizing conformation transitions of the Lipid II flippase MurJ
By Alvin C. Y. Kuk, Aili Hao, Z. Guan, Seok-Yong Lee. 2019
52 citations recorded by the source corpus.
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. MurJ is the flippase for the lipid-linked peptidoglycan precursor Lipid II, a key player in bacterial cell wall synthesis, but the flipping mechanism remains poorly understood. Here authors report crystal structures of MurJ in different conformations which shed light on the MurJ transitions that mediate lipid flipping.
Subfields: Molecular Biology
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In Molecular Biology
Citations in the corpus
- Sampling alternative conformational states of transporters and receptors with AlphaFold2 (2022, background): “…the class A GPCR CCR5 ( Zheng et al., 2017 ; Zhang et al., 2021 ), the serotonin transporter SERT ( Coleman et al., 2016 ; Coleman et al., 2019 ), the multidrug transporter PfMATE ( Tanaka et al., 2013 ; Zakrzewska et al., 2019 ), and the lipid flippase MurJ ( Kuk et al., 2017 ; Kuk et al., 2019 ).”