Simultaneous characterization of SNPs and N-glycans from multiple glycosylation sites of intact β-2-glycoprotein-1 (B2GP1) by ESI-qTOF-MS.

Authors:
Bernd Meyer
Bernd Meyer
Ruhr-Universität Bochum
Germany

Biochim Biophys Acta Proteins Proteom 2019 Jun 20;1867(6):556-564. Epub 2019 Mar 20.

Organic Chemistry, Department of Chemistry, University of Hamburg, Martin-Luther-King Platz 6, 20146 Hamburg, Germany. Electronic address:

The highly glycosylated ß-2-glycoprotein-1 (B2GP1), also called apolipoprotein H, is a 50 kDa human plasma protein with four or five N-glycosylation sites. Glycosylation of B2GP1 can impact auto antibody recognition leading to the development of antiphospholipid syndrome (APS), which can result in miscarriages or thrombosis. Next to its glycosylation different genetic variants are known to increase the risk of suffering from APS. Here we show that ESI-q/TOF-MS of intact B2GP1 can be used to analyze genetic variants and glycosylation simultaneously. After enrichment of B2GP1 from 16 different plasma samples and subsequent ESI-MS measurement of the intact protein, we detected five different SNPs in our samples either homozygous or heterozygous. The dominant glycan composition shows four biantennary, fully sialylated glycan structures, with a relative proportion of about 30%. We also detected compositions with one or two triantennary glycan structures in lower amounts and fucosylated species with one or two fucosyl residues. Two of our samples showed an unreported partially occupied fifth glycosylation site presumably arising from the presence of SNP variant S88N. Our method allows a fast determination of genetic variants and glycan compositions of human B2GP1 to be potentially used as diagnostic marker.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbapap.2019.03.007DOI Listing
June 2019
2 Reads

Article Mentions


Provided by Crossref Event Data
twitter
Twitter:
April 5, 2019, 9:05 am EST

Publication Analysis

Top Keywords

genetic variants
12
glycan structures
8
b2gp1
6
glycosylation
5
increase risk
4
30% detected
4
detected compositions
4
variants increase
4
proportion 30%
4
aps esi-q/tof-ms
4
esi-q/tof-ms intact
4
relative proportion
4
suffering aps
4
risk suffering
4
compositions triantennary
4
glycosylation genetic
4
syndrome aps
4
amounts fucosylated
4
fucosylated species
4
antiphospholipid syndrome
4

Similar Publications