Ontology highlight
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.
SUBMITTER: Ma C
PROVIDER: S-EPMC7732234 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Ma Cheng C Liu Ding D Li Dong D Zhang Junping J Xu Xiao-Qian XQ Zhu He H Wan Xiu-Feng XF Miao Carol H CH Konkle Barbara A BA Onigman Philip P Xiao Weidong W Li Lei L
Journal of thrombosis and haemostasis : JTH 20200614 8
<h4>Background/objective</h4>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 ...[more]