Glycopeptide specificity of the secretory protein folding sensor UDP-glucose glycoprotein:glucosyltransferase

EMBO Rep. 2003 Apr;4(4):405-11. doi: 10.1038/sj.embor.embor797.

Abstract

Secretory and membrane N-linked glycoproteins undergo folding and oligomeric assembly in the endoplasmic reticulum with the aid of a folding mechanism known as the calnexin cycle. UDP-glucose glycoprotein:glucosyltransferase (UGGT) is the sensor component of the calnexin cycle, which recognizes these glycoproteins when they are incompletely folded, and transfers a glucose residue from UDP-glucose to N-linked Man9-GlcNAc2 glycans. To determine how UGGT recognizes incompletely folded glycoproteins, we used purified enzyme to glucosylate a set of Man9-GlcNAc2 glycopeptide substrates in vitro, and determined quantitatively the glucose incorporation into each glycan by mass spectrometry. A ranked order of glycopeptide specificity was found that provides the criteria for the recognition of substrates by UGGT. The preference for amino-acid residues close to N-linked glycans provides criteria for the recognition of glycopeptide substrates by UGGT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Glucosyltransferases / chemistry
  • Glucosyltransferases / genetics
  • Glucosyltransferases / metabolism*
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry*
  • Glycoproteins / biosynthesis
  • Glycoproteins / chemistry
  • Kinetics
  • Molecular Sequence Data
  • Protein Folding
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology

Substances

  • Glycopeptides
  • Glycoproteins
  • Recombinant Proteins
  • Glucosyltransferases
  • mannosylglycoprotein 1,3-glucosyltransferase