Linked Life Data

19706343

Source:http://linkedlifedata.com/resource/pubmed/id/19706343

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-10-23
pubmed:abstractText
Beta2-glycoprotein I (beta2GPI) is a five-domain protein associated with the antiphospholipid syndrome (APS), however, its normal biological function is yet to be defined. beta2GPI 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 beta2GPI. The Gly40-Arg43 motif has also been proposed to serve as the epitope for the anti-beta2GPI 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-beta2GPI autoantibody. To test this hypothesis we used mass spectrometry (MS) for comparative glycopeptide profiling of human beta2GPI 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 beta2GPI 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 beta2GPI 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 beta2GPI and the pathology of antiphospholipid syndrome.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1876-7737
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-33
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Glycopeptide profiling of beta-2-glycoprotein I by mass spectrometry reveals attenuated sialylation in patients with antiphospholipid syndrome.
pubmed:affiliation
Protein Research Group, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't