Differential analysis of site-specific glycans on plasma and cellular fibronectins: application of a hydrophilic affinity method for glycopeptide enrichment

Glycobiology. 2005 Dec;15(12):1332-40. doi: 10.1093/glycob/cwj019. Epub 2005 Jul 21.

Abstract

Isolation of glycopeptides utilizing hydrogen bonding between glycopeptide glycans and a carbohydrate-gel matrix in the organic phase is useful for site-specific characterization of oligosaccharides of glycoproteins, when combined with mass spectrometry. In this study, recovery of glycopeptides was improved by including divalent cations or increasing the organic solvent in the binding solution, without losing specificity, whereas it was still less effective for those with a long peptide backbone exceeding 50 amino acid residues. The method was then applied to the analysis of glycan heterogeneities at seven N-glycosylation sites in each of the plasma and cellular fibronectins (FNs). There was a remarkable site-specific difference in fucosylation between these isoforms; Asn1244 selectively escaped the global fucosylation of cellular FN, whereas only Asn1007 and Asn2108 of the plasma isoform underwent modification. In addition, a new O-glycosylation site was identified at Thr279 in the connecting segment between the fibrin- and heparin-binding domain and the collagen-binding domain, and the glycopeptide was reactive to a peanut agglutinin lectin. Considering that another mucin-type O-glycosylation site lies within a different connecting segment, the O-glycosylation of FN was suggested to play a significant role in segregating the neighboring domains and thus maintaining the topology of FN and the domain functions. In addition, the method was applied to apolipoprotein B-100 (apoB100) whose N-glycan structures at 17 of 19 potential sites have been reported, and characterized the remaining sites. The results also demonstrated that the enriched glycopeptide provides resources for site-specific analysis of oligosaccharides in glycoproteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutinins / chemistry
  • Amino Acid Sequence
  • Apolipoprotein B-100
  • Apolipoproteins B / chemistry
  • Binding Sites
  • Cations
  • Chromatography
  • Chromatography, Affinity / methods*
  • Chromatography, High Pressure Liquid
  • Databases, Protein
  • Disulfides / chemistry
  • Fibrin / chemistry
  • Fibroblasts / metabolism
  • Fibronectins / blood*
  • Fibronectins / chemistry*
  • Glycopeptides / chemistry*
  • Glycosylation
  • Heparin / chemistry
  • Humans
  • Hydrogen Bonding
  • Lectins / chemistry
  • Mass Spectrometry
  • Molecular Sequence Data
  • Oligosaccharides / chemistry
  • Polysaccharides / chemistry*
  • Protein Binding
  • Protein Structure, Tertiary
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Threonine / chemistry
  • Time Factors
  • Transferrin / chemistry
  • Trypsin / chemistry

Substances

  • Agglutinins
  • Apolipoprotein B-100
  • Apolipoproteins B
  • Cations
  • Disulfides
  • Fibronectins
  • Glycopeptides
  • Lectins
  • Oligosaccharides
  • Polysaccharides
  • Transferrin
  • Threonine
  • Fibrin
  • Heparin
  • Trypsin