title: Mapping the N-glycome of human von Willebrand factor.
abstract: vWF (von Willebrand factor) is a key component for maintenance of normal haemostasis, acting as the carrier protein of the coagulant Factor VIII and mediating platelet adhesion at sites of vascular injury. There is ample evidence that vWF glycan moieties are crucial determinants of its expression and function. Of particular clinical interest, ABH antigens influence vWF plasma levels according to the blood group of individuals, although the molecular mechanism underlying this phenomenon remains incompletely understood. The present paper reports analyses of the human plasma vWF N-glycan population using advanced MS. Glycomics analyses revealed approximately 100 distinct N-glycan compositions and identified a variety of structural features, including lactosaminic extensions, ABH antigens and sulfated antennae, as well as bisecting and terminal GlcNAc residues. We estimate that some 300 N-glycan structures are carried by human vWF. Glycoproteomics analyses mapped ten of the consensus sites known to carry N-glycans. Glycan populations were found to be distinct, although many structural features were shared across all sites. Notably, the H antigen is not restricted to particular N-glycosylation sites. Also, the Asn(2635) site, previously designated as unoccupied, was found to be highly glycosylated. The delineation of such varied glycan populations in conjunction with current models explaining vWF activity will facilitate research aimed at providing a better understanding of the influence of glycosylation on vWF function.
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Hammersmith Hospital Campus, Imperial College, London, UK.
authors: Kevin
authors: K
authors: Canis
authors: Thomas A J
authors: TA
authors: McKinnon
authors: Agata
authors: A
authors: Nowak
authors: Stuart M
authors: SM
authors: Haslam
authors: Maria
authors: M
authors: Panico
authors: Howard R
authors: HR
authors: Morris
authors: Mike A
authors: MA
authors: Laffan
authors: Anne
authors: A
authors: Dell
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry; D002240:Carbohydrate Sequence; D054794:Glycomics / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014841:von Willebrand Factor / Q000737:chemistry*
chemical_list: D000942:Antigens, Bacterial; C022863:H antigen; D011134:Polysaccharides; D014841:von Willebrand Factor