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The ER glucosyltransferase reglucosylates non‐native and slow folding domains during glycoprotein maturation
Author(s) -
Pearse Bradley R.,
Gabriel Luke,
Hebert Daniel N.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a915-a
Subject(s) - chaperone (clinical) , endoplasmic reticulum , protein folding , glycoprotein , glycan , chemistry , calnexin , glucosyltransferase , endoplasmic reticulum associated protein degradation , microbiology and biotechnology , translocon , biochemistry , foldase , unfolded protein response , biology , membrane protein , calreticulin , enzyme , escherichia coli , medicine , pathology , groel , membrane , gene
The lectin endoplasmic reticulum (ER) quality control system acts to increase the fidelity of nascent glycoprotein folding within the ER. During the co‐translational translocation of the polypeptide into the ER, N‐linked glycans are transferred and glucose residues are immediately trimmed to facilitate lectin chaperone interactions. Removal of the terminal glucose ablates chaperone binding and the protein is prepared for export or reglucosylated by UDP‐glucose: glycoprotein glucosyltransferase (GT). Reglucosylation provides an opportunity for misfolded glycoproteins to attain their proper conformation or retain terminally misfolded proteins for degradation. Previous GT studies were largely performed in the absence of the specialized ER environment. Here, we used a mutant cell line that transfers Man9GlcNAc2 glycoforms. Thus, glucose addition to N‐linked glycans in the ER only occurs via GT reglucosylation. Using the substrate influenza hemagglutinin, we show that GT reglucosylates N‐linked glycans that support lectin chaperone binding in the slow folding stem domain once the nascent chain is released from the ribosome. In addition, these glycans are continually reglucosylated during post‐translational folding, indicating inherent targeting to this region. In contrast, the fast folding globular domain is not readily recognized by GT. Therefore, GT post‐translationally reglucosylates glycans on slow folding or non‐native domains for chaperone recruitment to critical regions. Supported by Public Health Service Grant CA79864 to D.N.H and a Chemistry‐Biology Interface NIH Training Grant T32GM008515 to B.R.P.