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O-Glycome beam search arrays for carbohydrate ligand discovery

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Title: O-Glycome beam search arrays for carbohydrate ligand discovery
Authors: Li, Z
Gao, C
Zhang, Y
Palma, A
Childs, R
Silva, L
Liu, Y
Jiang, X
Liu, Y
Chai, W
Feizi, T
Item Type: Journal Article
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 due to 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.
Issue Date: 28-Nov-2017
Date of Acceptance: 28-Nov-2017
URI: http://hdl.handle.net/10044/1/55198
DOI: https://dx.doi.org/10.1074/mcp.RA117.000285
ISSN: 1535-9476
Publisher: American Society for Biochemistry and Molecular Biology
Start Page: 121
End Page: 133
Journal / Book Title: Molecular and Cellular Proteomics
Volume: 17
Copyright Statement: © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
Wellcome Trust
Funder's Grant Number: 099197/Z/12/Z
108430/Z/15/Z
108430/Z/15/Z
Keywords: Array analysis
O-glycan
Omics
Rotaviruse
Sequencing MS
Tandem Mass Spectrometry
Thin Layer Chromatography
Viruses
MD Multidisciplinary
Biochemistry & Molecular Biology
Publication Status: Published online
Appears in Collections:Department of Medicine (up to 2019)