The plasma von Willebrand factor O-glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs.
BACKGROUND
von Willebrand factor (VWF) is a key component for maintenance of normal hemostasis. Its glycan moieties, accounting for about 20% of its molecular weight, have been shown to affect many of its properties. Previous studies reported correlations between VWF secretion, half-life and the nature or presence of its N-glycans, and more importantly between VWF plasma level and the type of N-linked ABH antigens. Despite the presence of 10 predicted O-glycosylation sites, the O-glycome remains poorly characterized, impairing the complete elucidation of its influence on VWF functions. So far only a single glycan structure, a disialyl core 1 glycan, has been identified.


OBJECTIVE
To define an exhaustive profile of the VWF O-glycan structures to help the understanding of their role in VWF regulation and properties.


METHODS
Plasma-derived VWF O-linked sugars were isolated and analyzed using state-of-the-art mass spectrometry methodologies.


CONCLUSIONS
We provide here a detailed analysis of the human plasma-derived VWF O-glycome. Eighteen O-glycan structures including both core 1 and core 2 structures are now demonstrated to be present on VWF. Amongst the newly determined structures are unusual tetra-sialylated core 1 O-glycans and ABH antigen-containing core 2 O-glycans. In conjunction with current models explaining VWF activity, knowledge of the complete O-glycome will facilitate research aimed at providing a better understanding of the influence of glycosylation on VWF functions.
Canis
K
K
Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College, London, UK.
McKinnon
T A J
TA
Nowak
A
A
Panico
M
M
Morris
H R
HR
Laffan
M
M
Dell
A
A
D000017:ABO Blood-Group System / Q000378:metabolism*; D020816:Amino Acid Motifs; D002236:Carbohydrate Conformation; D008401:Gas Chromatography-Mass Spectrometry; D054794:Glycomics / Q000379:methods; D006031:Glycosylation; D006801:Humans; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
D000017:ABO Blood-Group System; D014841:von Willebrand Factor