Abstract
Protein glycosylation is one of the most abundant post-translational modifications. However, detailed analysis of O-linked glycosylation, a major type of protein glycosylation, has been severely impeded by the scarcity of suitable methodologies. Here, a chemoenzymatic method is introduced for the site-specific extraction of O-linked glycopeptides (EXoO), which enabled the mapping of over 3,000 O-linked glycosylation sites and definition of their glycans on over 1,000 proteins in human kidney tissues, T cells, and serum. This large-scale localization of O-linked glycosylation sites demonstrated that EXoO is an effective method for defining the site-specific O-linked glycoproteome in different types of sample. Detailed structural analysis of the sites identified revealed conserved motifs and topological orientations facing extracellular space, the cell surface, the lumen of the Golgi, and the endoplasmic reticulum (ER). EXoO was also able to reveal significant differences in the O-linked glycoproteome of tumor and normal kidney tissues pointing to its broader use in clinical diagnostics and therapeutics.
Original language | English (US) |
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Article number | e8486 |
Journal | Molecular systems biology |
Volume | 14 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2018 |
Keywords
- O-GalNAc
- O-linked
- glycoproteomics
- glycosylation
- site-specific
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences
- Applied Mathematics