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Structural basis of lipopolysaccharide maturation by the WaaL O-antigen ligase
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(2022) Structural basis of lipopolysaccharide maturation by the WaaL O-antigen ligase. Nature, 604 . pp. 371-376. doi:10.1038/s41586-022-04555-x ISSN 0028-0836.
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WRAP-Structural-Lipopolysaccharide-maturation-O-antigen-ligase-2022.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only until 6 October 2023. Contact author directly, specifying your specific needs. - Requires a PDF viewer. Download (71Mb) |
Official URL: https://doi.org/10.1038/s41586-022-04555-x
Abstract
The outer membrane of Gram-negative bacteria has an external leaflet that is largely composed of lipopolysaccharide, which provides a selective permeation barrier, particularly against antimicrobials1. The final and crucial step in the biosynthesis of lipopolysaccharide is the addition of a species-dependent O-antigen to the lipid A core oligosaccharide, which is catalysed by the O-antigen ligase WaaL2. Here we present structures of WaaL from Cupriavidus metallidurans, both in the apo state and in complex with its lipid carrier undecaprenyl pyrophosphate, determined by single-particle cryo-electron microscopy. The structures reveal that WaaL comprises 12 transmembrane helices and a predominantly α-helical periplasmic region, which we show contains many of the conserved residues that are required for catalysis. We observe a conserved fold within the GT-C family of glycosyltransferases and hypothesize that they have a common mechanism for shuttling the undecaprenyl-based carrier to and from the active site. The structures, combined with genetic, biochemical, bioinformatics and molecular dynamics simulation experiments, offer molecular details on how the ligands come in apposition, and allows us to propose a mechanistic model for catalysis. Together, our work provides a structural basis for lipopolysaccharide maturation in a member of the GT-C superfamily of glycosyltransferases.
| Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Endotoxins, Electron microscopy -- Technique, Electron microscopy -- Methodology, Glycosyltransferases, Molecular biology, OAntigen | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Nature | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | Nature Publishing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 0028-0836 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Official Date: | 14 April 2022 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Volume: | 604 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 371-376 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1038/s41586-022-04555-x | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 21 February 2022 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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