Sequential analysis of N- and O-linked glycosylation of 2D-PAGE separated glycoproteins

J Proteome Res. 2002 Nov-Dec;1(6):521-9. doi: 10.1021/pr025538d.

Abstract

A robust method has been developed that allows analysis of both N- and O-linked oligosaccharides released from glycoproteins separated using 2D-PAGE and then electroblotted to PVDF membrane. This analysis provides efficient oligosaccharide profiling applicable to glycoproteomic analysis. The method involves the enzymatic release of N-linked oligosaccharides using PNGase F followed by the chemical release of O-linked oligosaccharides using reductive beta-elimination and analysis using LC-ESI-MS. Oligosaccharides from the major plasma glycoproteins with a pI between 4 and 7 were characterized from the glycoforms of haptoglobin, alpha2-HS-glycoprotein, serotransferrin, alpha1-antitrypsin, and alpha1-antichymotrypsin. It was shown that the separation of protein glycoforms evident in 2D-PAGE is partially due to the combined sialylation of the O-linked and N-linked oligosaccharides. Bi-, tri- and tetra-antennary N-linked structures, which had differing levels of sialylation and fucosylation, were found to be present on the glycoproteins analyzed, together with O-linked oligosaccharides such as mono-, and disialylated T-antigen and a disialylated core type 2 hexasaccharide. In addition, N-linked site-specific information was obtained by MALDI-MS analysis using tryptic digestion after PNGase F release of the oligosaccharides.

MeSH terms

  • Amidohydrolases / metabolism
  • Electrophoresis, Gel, Two-Dimensional*
  • Electrophoresis, Polyacrylamide Gel*
  • Flavobacterium
  • Glycoproteins / analysis*
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism
  • Glycosylation*
  • Humans
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Trypsin / metabolism

Substances

  • Glycoproteins
  • Trypsin
  • Amidohydrolases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase