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Recent advances in demystifying O-glycosylation in health and disease
Jiajia Li1, Bo Guo2, Wenqi Zhang1
1Center for Clinical Mass Spectrometry, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Abstract:
O-Glycosylation is one of the most common protein post-translational modifications (PTM) and plays an essential role in the pathophysiology of diseases. However, the complexity of O-glycosylation and the lack of specific enzymes for the processing of O-glycans and their O-glycopeptides make O-glycosylation analysis challenging. Recently, research on O-glycosylation has received attention owing to technological innovation and emerging O-glycoproteases. Several serine/threonine endoproteases have been found to specifically cleave O-glycosylated serine or threonine, allowing for the systematic analysis of O-glycoproteins. In this review, we first assessed the field of protein O-glycosylation over the past decade and used bibliometric analysis to identify keywords and emerging trends. We then summarized recent advances in O-glycosylation, covering several aspects: O-glycan release, site-specific elucidation of intact O-glycopeptides, identification of O-glycosites, characterization of different O-glycoproteases, mass spectrometry (MS) fragmentation methods for site-specific O-glycosylation assignment, and O-glycosylation data analysis. Finally, the role of O-glycosylation in health and disease was discussed.
Insights
O-glycosylation, a key protein modification in disease, is now more analyzable due to new O-glycoproteases. This review highlights advances in O-glycopeptide analysis and the role of O-glycosylation in health and disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Glycobiology
Background:
- O-glycosylation is a prevalent post-translational modification (PTM) crucial in disease pathophysiology.
- The complexity and lack of specific enzymes have historically hindered O-glycosylation analysis.
- Recent technological innovations and the discovery of O-glycoproteases are advancing the field.
Purpose of the Study:
- To review the progress in protein O-glycosylation analysis over the last decade.
- To identify emerging trends and keywords in O-glycosylation research using bibliometric analysis.
- To summarize recent advancements in O-glycosylation methodologies and discuss its role in health and disease.
Main Methods:
- Bibliometric analysis of O-glycosylation literature.
- Review of recent advancements in O-glycan release and O-glycopeptide analysis.
- Discussion of O-glycoprotease characterization and mass spectrometry (MS) based identification methods.
Main Results:
- Bibliometric analysis identified key trends and keywords in O-glycosylation research.
- Significant progress has been made in site-specific O-glycopeptide elucidation and O-glycosite identification.
- Characterization of O-glycoproteases and advanced MS fragmentation techniques facilitate detailed O-glycosylation analysis.
Conclusions:
- Technological advancements, particularly O-glycoproteases, have overcome previous challenges in O-glycosylation analysis.
- Systematic analysis of O-glycoproteins is now feasible, enabling deeper understanding of their roles.
- Further research into O-glycosylation is critical for understanding its impact on health and disease.
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