O-Glycome Beam Search Arrays for Carbohydrate Ligand Discovery.

Autor: Li Z; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK., Gao C; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK.; §Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215., Zhang Y; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK., Palma AS; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK.; ¶Department of Chemistry, UCIBIO-NOVA University of Lisbon, 1099085, Portugal., Childs RA; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK., Silva LM; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK., Liu Y; ‖Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center and., Jiang X; ‖Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center and.; *University of Cincinnati College of Medicine, Cincinnati, Ohio 45229., Liu Y; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK., Chai W; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK; t.feizi@imperial.ac.uk w.chai@imperial.ac.uk., Feizi T; From the ‡Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN, UK; t.feizi@imperial.ac.uk w.chai@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Molecular & cellular proteomics : MCP [Mol Cell Proteomics] 2018 Jan; Vol. 17 (1), pp. 121-133. Date of Electronic Publication: 2017 Nov 28.
DOI: 10.1074/mcp.RA117.000285
Abstrakt: 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.
(© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze: MEDLINE