N-glycosylation efficiency is determined by the distance to the C-terminus and the amino acid preceding an Asn-Ser-Thr sequon

Protein Sci. 2011 Jan;20(1):179-86. doi: 10.1002/pro.551.

Abstract

N-glycosylation is the most common and versatile protein modification. In eukaryotic cells, this modification is catalyzed cotranslationally by the enzyme oligosaccharyltransferase, which targets the β-amide of the asparagine in an Asn-Xaa-Ser/Thr consensus sequon (where Xaa is any amino acid but proline) in nascent proteins as they enter the endoplasmic reticulum. Because modification of the glycosylation acceptor site on membrane proteins occurs in a compartment-specific manner, the presence of glycosylation is used to indicate membrane protein topology. Moreover, glycosylation sites can be added to gain topological information. In this study, we explored the determinants of N-glycosylation with the in vitro transcription/translation of a truncated model protein in the presence of microsomes and surveyed 25,488 glycoproteins, of which 2,533 glycosylation sites had been experimentally validated. We found that glycosylation efficiency was dependent on both the distance to the C-terminus and the nature of the amino acid that preceded the consensus sequon. These findings establish a broadly applicable method for membrane protein tagging in topological studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Cell-Free System
  • Consensus Sequence
  • Dogs
  • Escherichia coli Proteins / metabolism
  • Glycosylation
  • In Vitro Techniques
  • Membrane Proteins / metabolism*
  • Microsomes / metabolism
  • Protein Modification, Translational*
  • Rabbits
  • Recombinant Proteins / metabolism
  • Serine Endopeptidases / metabolism*

Substances

  • Escherichia coli Proteins
  • Membrane Proteins
  • Recombinant Proteins
  • Serine Endopeptidases
  • type I signal peptidase