Protein glycosylation analysis by HILIC-LC-MS of Proteinase K-generated N- and O-glycopeptides

J Sep Sci. 2010 Mar;33(6-7):903-10. doi: 10.1002/jssc.200900850.

Abstract

Analysis of protein glycosylation is essential in order to correlate certain disease types with oligosaccharide structures on proteins. Here, a method for the MS characterization of site-specific protein glycosylation is presented. Using asialofetuin and fetuin as model substances, a protocol for glycopeptide dissection was developed based on unspecific proteolysis by Proteinase K. The resulting glycopeptides were then resolved by nanoscale hydrophilic interaction liquid chromatography-electrospray multistage MS. The early elution range of O-glycopeptides was clearly separated from the late elution range of N-glycopeptides. Glycopeptides were analyzed by ion trap-MS/MS, which revealed fragmentations of glycosidic linkages and some peptide backbone cleavages; MS(3) spectra predominantly exhibited cleavages of the peptide backbone and provided essential information on the peptide sequence. The previously reported N- and O-glycan attachment sites of fetuin could be confirmed; moreover using our method, the occupation of a new, additional O-glycosylation site serine 296 was found. In conclusion, this approach appears to be a valuable technique for in-depth analysis of the site-specific N-glycosylation and O-glycosylation of individual glycoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, Liquid / methods*
  • Endopeptidase K / chemistry*
  • Glycopeptides / chemistry*
  • Glycosylation
  • Nanotechnology
  • Proteins / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Glycopeptides
  • Proteins
  • Endopeptidase K