An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells

Research output: Contribution to journalJournal articleResearchpeer-review

  • Richard Karlsson
  • Lingbo Sun
  • Zilu Ye
  • Catharina Steentoft
  • Sanae Furukawa
  • Barbara A. Bensing
  • Paul M. Sullam
  • Andrew J. Thompson
  • James C. Paulson
  • Christian Büll
  • Gosse J. Adema
  • Ajit Varki

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.

Original languageEnglish
JournalMolecular Cell
Issue number2
Pages (from-to)394-407, e1-e5
Publication statusPublished - 2019

Bibliographical note

Copyright © 2019 Elsevier Inc. All rights reserved.

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