Visualizing conformation transitions of the Lipid II flippase MurJ.
Journal Article (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
- PMC6465408
Electronic International Standard Serial Number (EISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/s41467-019-09658-0
Language
- eng
Conference Location
- England