ArticleScientific reports2017
Structural basis of inhibition of lipid-linked oligosaccharide flippase PglK by a conformational nanobody.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Mass Photometry Analysis of Membrane Proteins in Detergent Micelles.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The Glycoworld: Glycoproteins in Nature: A General Overview of the Different Roles That Glycoproteins Exert in Living Organism.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Structure of WzxE the lipid III flippase for Enterobacterial Common Antigen polysaccharide.Open biology · 2025Article
- Structural and mechanistic studies of the N-glycosylation machinery: from lipid-linked oligosaccharide biosynthesis to glycan transfer.Glycobiology · 2023Review
- Insights into Membrane Curvature Sensing and Membrane Remodeling by Intrinsically Disordered Proteins and Protein Regions.The Journal of membrane biology · 2022Review
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
- Mechanics and pharmacology of substrate selection and transport by eukaryotic ABC exporters.Nature structural & molecular biology · 2019Review
- Identification of conformation-selective nanobodies against the membrane protein insertase BamA by an integrated structural biology approach.Journal of biomolecular NMR · 2019Article
- The extracellular gate shapes the energy profile of an ABC exporter.Nature communications · 2019Article
- Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.Nature communications · 2018Article
- Article
- Intramembranal disulfide cross-linking elucidates the super-quaternary structure of mammalian CatSpers.Reproductive biology · 2018Article
- Boosted coupling of ATP hydrolysis to substrate transport upon cooperative estradiol-17-β-D-glucuronide binding in a Drosophila ATP binding cassette type-C transporter.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PglK is an ABC transporter that flips a lipid-linked oligosaccharide (LLO) that serves as a donor in protein N-glycosylation. Previous structures revealed two inward-facing conformations, both with very large separations of the nucleotide binding domains (NBDs), and a closed, ADP-bound state that featured an occluded cavity. To investigate additional states, we developed conformation-sensitive, single-domain camelid nanobodies (Nb) and studied their effect on PglK activity. Biochemical, structural, and mass spectrometric analyses revealed that one inhibitory Nb binds as a single copy to homodimeric PglK. The co-crystal structure of this Nb and ADP-bound PglK revealed a new, narrowly inward-open conformation. Rather than inducing asymmetry in the PglK homodimer, the binding of one Nb results in steric constraints that prevent a second Nb to access the symmetry-related site in PglK. The Nb performed its inhibitory role by a "sticky-doorstop" mechanism, where inhibition of ATP hydrolysis and LLO flipping activity occurs due to impaired closing of the NBD interface, which prevents PglK from converting to an outward-open conformation. This inhibitory mode suggests tight conformational coupling between the ATPase sites, which may apply to other ABC transporters.
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