Publication Abstract from PubMed
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.
The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase modifies substrates distant to local changes in glycoprotein conformation.,Taylor SC, Ferguson AD, Bergeron JJ, Thomas DY Nat Struct Mol Biol. 2004 Feb;11(2):128-34. Epub 2004 Jan 4. PMID:14730348[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
