Folding of synthetic homogeneous glycoproteins in the presence of a glycoprotein folding sensor enzyme

Angew Chem Int Ed Engl. 2014 Mar 10;53(11):2883-7. doi: 10.1002/anie.201309665. Epub 2014 Feb 5.

Abstract

UDP-glucose:glycoprotein glucosyltransferase (UGGT) plays a key role in recognizing folded and misfolded glycoproteins in the glycoprotein quality control system of the endoplasmic reticulum. UGGT detects misfolded glycoproteins and re-glucosylates them as a tag for misfolded glycoproteins. A flexible model to reproduce in vitro folding of a glycoprotein in the presence of UGGT in a mixture containing correctly folded, folding intermediates, and misfolded glycoproteins is described. The data demonstrates that UGGT can re-glucosylate all intermediates in the in vitro folding experiments, thus indicating that UGGT inspects not only final folded products, but also the glycoprotein folding intermediates.

Keywords: biological activity; glycoproteins; mass spectrometry; molecular recognition; protein folding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • Glucosyltransferases / chemistry*
  • Glucosyltransferases / metabolism*
  • Humans
  • Plant Proteins / chemistry
  • Plant Proteins / metabolism
  • Protein Folding
  • Spectrometry, Mass, Electrospray Ionization
  • Substrate Specificity

Substances

  • Plant Proteins
  • crambin protein, Crambe abyssinica
  • Glucosyltransferases
  • mannosylglycoprotein 1,3-glucosyltransferase