Population studies of Vitamin D Binding Protein microheterogeneity by mass spectrometry lead to characterization of its genotype-dependent O-glycosylation patterns.
Mass spectrometric evidence presented here characterizes the genotype-dependent glycosylation patterns for each of the three major allele products of Vitamin D Binding Protein found in the general human population. Findings based on the analysis of over 100 individual plasma samples demonstrated that all DBP allele products, except GC*2, are modified (10-25 mol%) with a linear (NeuNAc) 1(Gal) 1(GalNAc) 1 trisaccharide and, to a much lesser extent (1-5 mol%) with a trisaccharide-independent (Gal) 1(GalNAc) 1 dissaccharide. GC*2 protein contains the disaccharide but remains completely free of the trisaccharide, even in heterozygous individuals possessing a second gene product that is modified with the trisaccharide. Thus, all allelic forms of DBP except GC*2 possess two independent O-glycosylation sites occupied by separate, yet consistently isomass oligosaccharides and, despite a consensus sequence, lack N-glycosylation.
Borges
Chad R
CR
Molecular Biosignatures Analysis Unit, The Biodesign Institute at Arizona State University, Tempe, AZ 85287, USA. chad.borges@asu.edu
Jarvis
Jason W
JW
Oran
Paul E
PE
Nelson
Randall W
RW
D000595:Amino Acid Sequence; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011159:Population Surveillance; D020543:Proteome; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014809:Vitamin D-Binding Protein / Q000737:chemistry*
D020543:Proteome; D014809:Vitamin D-Binding Protein