7tpj

Single-Particle Cryo-EM Structure of the WaaL O-antigen ligase in its apo state

spinqualitylabelsall models 7tpj, resolution 3.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7tpj is a 3 chain structure with sequence from Cupriavidus metallidurans and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.46Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q1LJU1_CUPMC Publication Abstract from PubMed 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 antimicrobials(1). 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 WaaL(2). 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 alpha-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. Structural basis of lipopolysaccharide maturation by the O-antigen ligase.,Ashraf KU, Nygaard R, Vickery ON, Erramilli SK, Herrera CM, McConville TH, Petrou VI, Giacometti SI, Dufrisne MB, Nosol K, Zinkle AP, Graham CLB, Loukeris M, Kloss B, Skorupinska-Tudek K, Swiezewska E, Roper DI, Clarke OB, Uhlemann AC, Kossiakoff AA, Trent MS, Stansfeld PJ, Mancia F Nature. 2022 Apr;604(7905):371-376. doi: 10.1038/s41586-022-04555-x. Epub 2022 , Apr 6. PMID:35388216 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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