AI Article Synopsis
- The glycoprotein quality control (GQC) system in the endoplasmic reticulum (ER) utilizes enzymes and lectins to ensure that glycoproteins fold correctly from their initial polypeptide form, though the exact molecular processes involved are still not fully understood.
- Researchers synthesized specific glycoproteins and their misfolded versions to investigate the GQC process, using analytical techniques like high performance liquid chromatography and mass spectrometry to observe the refolding dynamics.
- Their findings indicate that the GQC system operates in a catalytic cycle that rapidly alternates between glucosylation and deglucosylation, effectively promoting the refolding of misfolded glycoproteins.
Article Abstract
The glycoprotein quality control (GQC) system in the endoplasmic reticulum (ER) effectively uses chaperone-type enzymes and lectins such as UDP-glucose:glycoprotein glucosyltransferase (UGGT), calnexin (CNX), calreticulin (CRT), protein disulfide bond isomerases (ERp57 or PDIs), and glucosidases to generate native-folded glycoproteins from nascent glycopolypeptides. However, the individual processes of the GQC system at the molecular level are still unclear. We chemically synthesized a series of several homogeneous glycoproteins bearing M9-high-mannose type oligosaccharides (M9-glycan), such as erythropoietin (EPO), interferon-β (IFN-β), and interleukin 8 (IL8) and their misfolded counterparts, and used these glycoprotein probes to better understand the GQC process. The analyses by high performance liquid chromatography and mass spectrometer clearly showed refolding processes from synthetic misfolded glycoproteins to native form through folding intermediates, allowing for the relationship between the amount of glucosylation and the refolding of the glycoprotein to be estimated. The experiment using these probes demonstrated that GQC system isolated from rat liver acts in a catalytic cycle regulated by the fast crosstalk of glucosylation/deglucosylation in order to accelerate refolding of misfolded glycoproteins.
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| http://dx.doi.org/10.1021/jacs.8b08653 | DOI Listing |
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