The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase modifies substrates distant to local changes in glycoprotein conformation - PubMed (original) (raw)

doi: 10.1038/nsmb715. Epub 2004 Jan 4.

Affiliations

PMID: 14730348
DOI: 10.1038/nsmb715

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

Sean C Taylor et al. Nat Struct Mol Biol. 2004 Feb.

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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Insights into checkpoint capacity.
Sifers RN. Sifers RN. Nat Struct Mol Biol. 2004 Feb;11(2):108-9. doi: 10.1038/nsmb0204-108. Nat Struct Mol Biol. 2004. PMID: 14749767 No abstract available.

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The ER protein folding sensor UDP-glucose glycoprotein-glucosyltransferase modifies substrates distant to local changes in glycoprotein conformation - PubMed (original) (raw)