期刊
ACS CHEMICAL BIOLOGY
卷 16, 期 10, 页码 1866-1883出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.1c00384
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资金
- Yale Science Development Fund
- Yale SEAS/Science Program to Advance Research Collaboration (SPARC)
This review summarizes recent advancements in the study of mucin-domain glycoproteins, highlighting their roles in diseases, challenges, and new opportunities for research in this area.
Mucin-domain glycoproteins comprise a class of proteins whose densely O-glycosylated mucin domains adopt a secondary structure with unique biophysical and biochemical properties. The canonical family of mucins is well-known to be involved in various diseases, especially cancer. Despite this, very little is known about the site-specific molecular structures and biological activities of mucins, in part because they are extremely challenging to study by mass spectrometry (MS). Here, we summarize recent advancements toward this goal, with a particular focus on mucin-domain glycoproteins as opposed to general O-glycoproteins. We summarize proteolytic digestion techniques, enrichment strategies, MS fragmentation, and intact analysis, as well as new bioinformatic platforms. In particular, we highlight mucin directed technologies such as mucin-selective proteases, tunable mucin platforms, and a mucinomics strategy to enrich mucin-domain glycoproteins from complex samples. Finally, we provide examples of targeted mucin-domain glycoproteomics that combine these techniques in comprehensive site-specific analyses of proteins. Overall, this Review summarizes the methods, challenges, and new opportunities associated with studying enigmatic mucin domains.
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