ArticleNature2015
Structure and mechanism of an active lipid-linked oligosaccharide flippase.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 203 citations in OpenAlex.
- Recognition and mechanism of M. tuberculosis cell wall galactan transport.Nature communications · 2026Article
- Mass Photometry Analysis of Membrane Proteins in Detergent Micelles.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction Factor.bioRxiv : the preprint server for biology · 2025Article
- Structural insights into polyisoprenyl-binding glycosyltransferases.Structure (London, England : 1993) · 2025Review
- The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.Nature communications · 2025Article
- Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide.Open biology · 2025Article
- Structures of the Mycobacterium tuberculosis efflux pump EfpA reveal the mechanisms of transport and inhibition.Nature communications · 2024Article
- Lipid scrambling is a general feature of protein insertases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structures of the essential efflux pump EfpA fromResearch square · 2024Article
- The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains.The Journal of biological chemistry · 2024Article
- Structural and mechanistic studies of the N-glycosylation machinery: from lipid-linked oligosaccharide biosynthesis to glycan transfer.Glycobiology · 2023Review
- Article
- Lipid scrambling is a general feature of protein insertases.bioRxiv : the preprint server for biology · 2023Article
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- Article
- Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A.Nature communications · 2023Article
- Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB.Protein & cell · 2023Article
- Relevance of Sugar Transport across the Cell Membrane.International journal of molecular sciences · 2023Review
- Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP.Signal transduction and targeted therapy · 2023Article
- The culmination of multidrug-resistant efflux pumps vs. meager antibiotic arsenal era: Urgent need for an improved new generation of EPIs.Frontiers in microbiology · 2023Review
54 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N-linked protein glycosylation. In Campylobacter jejuni, this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro, but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.