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The plasma von Willebrand factor O ‐glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs
Author(s) -
CANIS K.,
MCKIN T. A. J.,
NOWAK A.,
PANICO M.,
MORRIS H. R.,
LAFFAN M.,
DELL A.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03665.x
Subject(s) - glycome , von willebrand factor , computational biology , biology , glycan , immunology , genetics , glycoprotein , platelet
Summary. 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. Objectives : 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. Results and 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.