O-glycome beam search arrays for carbohydrate ligand discovery

Zhen Li, Chao Gao, Yibing Zhang, Angelina S. Palma, Robert A. Childs, Lisete M. Silva, Yang Liu, Xi Jiang, Yan Liu, Wengang Chai, Ten Feizi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

O-glycosylation is a post-translational modification of proteins crucial to molecular mechanisms in health and disease. O-glycans are typically highly heterogeneous. The involvement of specific O-glycan sequences in many bio-recognition systems is yet to be determined because of a lack of efficient methodologies. We describe here a targeted microarray approach: O-glycome beam search that is both robust and efficient for O-glycan ligand-discovery. Substantial simplification of the complex O-glycome profile and facile chromatographic resolution is achieved by arraying O-glycans as branches, monitoring by mass spectrometry, focusing on promising fractions, and on-array immuno-sequencing. This is orders of magnitude more sensitive than traditional methods. We have applied beam search approach to porcine stomach mucin and identified extremely minor components previously undetected within the O-glycome of this mucin that are ligands for the adhesive proteins of two rotaviruses. The approach is applicable to O-glycome recognition studies in a wide range of biological settings to give insights into glycan recognition structures in natural microenvironments.

Original languageEnglish
Pages (from-to)121-133
Number of pages13
JournalMolecular and Cellular Proteomics
Volume17
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

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