Journal
MOLECULAR CELL
Volume 75, Issue 2, Pages 394-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2019.05.017
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Funding
- Lundbeck Foundation
- Novo Nordisk Foundation
- Kirsten og Freddy Johansens Fond
- A.P. Moller Fonden
- Laege Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat
- European Commission [GlycoImaging H2020-MSCA-ITN-721297, BioCapture H2020-MSCA-ITN-722171]
- NIH [AI114730, R01AI41513, R01AI106987, U01OD024857]
- Kuang Hua Educational Foundation
- Danish National Research Foundation [DNRF107]
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The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates. We used maps of glycosylation pathways to generate a library of isogenic HEK293 cells with combinatorially engineered glycosylation capacities designed to display and dissect the genetic, biosynthetic, and structural basis for glycan binding in a natural context. The cell-based glycan array is self-renewable and reports glycosyltransferase genes required (or blocking) for interactions through logical sequential biosynthetic steps, which is predictive of structural glycan features involved and provides instructions for synthesis, recombinant production, and genetic dissection strategies. Broad utility of the cell-based glycan array is demonstrated, and we uncover higher order binding of microbial adhesins to clustered patches of O-glycans organized by their presentation on proteins.
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