The ER protein folding sensor UDP-glucose glycoprotein–glucosyltransferase modifies substrates distant to local changes in glycoprotein conformation

被引:0
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作者
Sean C Taylor
Andrew D Ferguson
John J M Bergeron
David Y Thomas
机构
[1] Faculty of Medicine,Biochemistry Department
[2] McGill University,Department of Anatomy and Cell Biology
[3] McIntyre Medical Sciences Building,Department of Biochemistry
[4] 3655 Boulevard Sir William Osler,undefined
[5] McGill University,undefined
[6] Montreal Proteomics Network,undefined
[7] Genome Quebec Innovation Centre,undefined
[8] McGill University,undefined
[9] University of Texas Southwestern Medical Center,undefined
来源
Nature Structural & Molecular Biology | 2004年 / 11卷
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摘要
We present in vitro data that explain the recognition mechanism of misfolded glycoproteins by UDP-glucose glycoprotein–glucosyltransferase (UGGT). The glycoprotein exo-(1,3)-β-glucanase (β-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 β-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 Å from localized regions of disorder and sense subtle conformational changes within structurally compact, enzymatically active glycoprotein substrates.
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页码:128 / 134
页数:6
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