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3123768 
Journal Article 
Hydrophobic Tagged Dihydrofolate Reductase for Creating Misfolded Glycoprotein Mimetics 
Hachisu, M; Seko, A; Daikoku, S; Takeda, Y; Sakono, M; Ito, Y 
2016 
Yes 
ChemBiochem
ISSN: 1439-4227
EISSN: 1439-7633 
WILEY-V C H VERLAG GMBH 
WEINHEIM 
17 
4 
300-303 
English 
26670196 
WOS:000370656900006 
In the endoplasmic reticulum (ER), nascent glycoproteins that have not acquired the native conformation are either repaired or sorted for degradation by specific quality-control systems composed by various proteins. Among them, UDP-glucose:glycoprotein glucosyltransferase (UGGT) serves as a folding sensor in the ER. However, the molecular mechanism of its recognition remains obscure. This study used pseudo-misfolded glycoproteins, comprising a modified dihydrofolate reductase with artificial pyrene-cysteine moiety on the protein surface (pDHFR) and Man9 GlcNAc2 -methotrexate (M9-MTX). All five M9-MTX/pDHFR complexes, with a pyrene group at different positions, were found to be good substrates of UGGT, irrespective of the site of pyrene modification. These results suggest UGGT's mode of substrate recognition is fuzzy, thus allowing various glycoproteins to be accommodated in the folding cycle. 
DHFR; enzyme catalysis; ER-quality control; glycoproteins; high-mannose-type glycan; UGGT