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Updated: Aug 29, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
Published on: June 14, 2024
The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase modifies substrates distant to local
Sean C Taylor1, Andrew D Ferguson, John J M Bergeron
1Biochemistry Department, Faculty of Medicine, McGill University, McIntyre Medical Sciences Building, 3655 Boulevard Sir William Osler, Montreal, Quebec, Canada, H3G 1Y6.
Abstract:
We present in vitro data that explain the recognition mechanism of misfolded glycoproteins by UDP-glucose glycoprotein-glucosyltransferase (UGGT). The glycoprotein exo-(1,3)-beta-glucanase (beta-Glc) bearing two glycans unfolds in a pH-dependent manner to become a misfolded substrate for UGGT. In the crystal structure of this glycoprotein, the local hydrophobicity surrounding each glycosylation site coincides with the differential recognition of N-linked glycans by UGGT. We introduced a single F280S point mutation, producing a beta-Glc protein with full enzymatic activity that was both recognized as misfolded and monoglucosylated by UGGT. Contrary to current views, these data show that UGGT can modify N-linked glycans positioned at least 40 A from localized regions of disorder and sense subtle conformational changes within structurally compact, enzymatically active glycoprotein substrates.
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