Visualizing conformation transitions of the Lipid II flippase MurJ.

Publication Type:

Journal Article

Source:

Nat Commun, Volume 10, Issue 1, p.1736 (2019)

Abstract:

<p>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.</p>

PDB: 
6NC6, 6NC7, 6NC8, and 6NC9
Detector: 
PILATUS
EIGER
Beamline: 
24-ID-C
24-ID-E