Recognition of local glycoprotein misfolding by the ER folding sensor UDP-glucose:glycoprotein glucosyltransferase.
The endoplasmic reticulum (ER) contains a stringent quality control system that ensures the correct folding of newly synthesized proteins to be exported via the secretory pathway. In this system UDP-Glc:glycoprotein glucosyltransferase (GT) serves as a glycoprotein specific folding sensor by specifically glucosylating N-linked glycans in misfolded glycoproteins thus retaining them in the calnexin/calreticulin chaperone cycle. To investigate how GT senses the folding status of glycoproteins, we generated RNase B heterodimers consisting of a folded and a misfolded domain. Only glycans linked to the misfolded domain were found to be glucosylated, indicating that the enzyme recognizes folding defects at the level of individual domains and only reglucosylates glycans directly attached to a misfolded domain. The result was confirmed with complexes of soybean agglutinin and misfolded thyroglobulin.
Ritter
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Institute of Biochemistry, Swiss Federal Institute of Technology, Universitaetstr. 16, CH-8092 Zurich, Switzerland.
Helenius
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D000478:Alkylation; D000818:Animals; D002417:Cattle; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism*; D005964:Glucosyltransferases / Q000378:metabolism*; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D006031:Glycosylation; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D016877:Oxidants / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D037121:Plant Lectins; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D019163:Reducing Agents / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D030262:Soybean Proteins; D013379:Substrate Specificity; D020860:Subtilisin / Q000378:metabolism; D013954:Thyroglobulin / Q000737:chemistry / Q000378:metabolism; D010835:Phytohemagglutinins
D005964:Glucosyltransferases; D006023:Glycoproteins; D037102:Lectins; D016877:Oxidants; D010446:Peptide Fragments; D037121:Plant Lectins; D011134:Polysaccharides; D019163:Reducing Agents; D012260:Ribonucleases; D030262:Soybean Proteins; D020860:Subtilisin; D013954:Thyroglobulin; C028824:soybean lectin; D010835:Phytohemagglutinins; C072423:mannosylglycoprotein 1,3-glucosyltransferase