Visualizing conformation transitions of the Lipid II flippase MurJ.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kuk, ACY; Hao, A; Guan, Z; Lee, S-Y

Published Date

  • April 15, 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 1736 -

PubMed ID

  • 30988294

Pubmed Central ID

  • 30988294

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-09658-0

Language

  • eng

Conference Location

  • England