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Comprehensive N‐ and O‐glycosylation mapping of human coagulation factor V

Comprehensive N‐ and O‐glycosylation mapping of human coagulation factor V

Authors :
Junping Zhang
Carol H. Miao
Lei Li
Xiao-Qian Xu
Philip Onigman
Cheng Ma
Ding Liu
Barbara A. Konkle
He Zhu
Xiu-Feng Wan
Weidong Xiao
Dong Li
Source :
J Thromb Haemost
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Background/objective Coagulation factor V (FV), a multidomain glycoprotein, is an essential cofactor in the blood clotting cascade. FV deficiency is a rare bleeding disorder that results in poor clotting after an injury or surgery. The only treatment for the disease is infusions of fresh frozen plasma and blood platelets. Glycosylation affects the biological activity, pharmacokinetics, immunogenicity, and in vivo clearance rate of proteins in the plasma. The glycan profile of FV, as well as how it affects the activity, stability, and immunogenicity, remains unknown. Methods In this study, we comprehensively mapped the glycosylation patterns of human plasma-derived FV by combining multienzyme digestion, hydrophilic interaction chromatography enrichment of glycopeptides, and alternated fragmentation mass spectrometry analysis. Results/conclusion A total of 57 unique N-glycopeptides and 51 O-glycopeptides were identified, which were categorized into 40 N-glycan and 17 O-glycan compositions. Such glycosylation details are fundamental for future functional studies and therapeutics development. In addition, the established methodology can be readily applied to analyze glycosylation patterns of proteins with more than 2000 amino acids.

Details

ISSN :
15387836
Volume :
18
Database :
OpenAIRE
Journal :
Journal of Thrombosis and Haemostasis
Accession number :
edsair.doi.dedup.....f22294b2b886ad0f39aa4557294735e2
Full Text :
https://doi.org/10.1111/jth.14861