Comprehensive N- and O-glycosylation mapping of human coagulation factor V.
J Thromb Haemost
; 18(8): 1884-1892, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32310329
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator V
/
Glicopeptídeos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos