期刊
JOURNAL OF PROTEOMICS
卷 73, 期 1, 页码 123-133出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jprot.2009.08.007
关键词
beta 2-glycoprotein I; Antiphospholipid syndrome; N-glycan; MALDI-MS; LC-ESI-MS; In-source decay
资金
- Danish Research Agency
- Lundbeck Foundation Research Professor
beta 2-glycoprotein I (beta 2GPI) is a five-domain protein associated with the antiphospholipid syndrome (APS), however, its normal biological function is yet to be defined. beta 2GPI is N-glycosylated at several asparagine residues and the glycan moiety conjugated to residue 143 has been proposed to interact with the Gly40-Arg43 motif of beta 2GPI. The Gly40-Arg43 motif has also been proposed to serve as the epitope for the anti-beta 2GPI autoantibody associated with APS. We hypothesized that the structure or composition of the glycan at Asn-143 might be associated with the APS symptom by shielding or exposing the Gly40-Arg43 motif towards the anti-beta 2GPI autoantibody. To test this hypothesis we used mass spectrometry (MS) for comparative glycopeptide profiling of human beta 2GPI obtained from blood serum from four healthy test subjects and six APS patients. it revealed significant differences in the extent of sialylation and branching of glycans at Asn-143. Biantennary glycans were more abundant than triantennary glycans at Asn-143 in both healthy subjects and patients. in APS patient samples we observed a decrease in sialylated triantennary glycans and an increase in sialylated biantennary glycan structures, as compared to controls. These data indicate that some APS patients have beta 2GPI molecules with a reduced number of negatively charged sialic acid units in the glycan structure at Asn-143. This alteration of the electrostatic properties of the glycan moiety may attenuate the intramolecular interactions with the positively charged Gly40-Arg43 motif of beta 2GPI and, in turn, leads to conformational instability and exposure of the disease-related linear epitope Gly40-Arg43 to the circulating autoantibody. Thus, our study suggests a link between site-specific glycan profiles of beta 2GPI and the pathology of antiphospholipid syndrome. (C) 2009 Elsevier B.V. All rights reserved.
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