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N-glycan structure dictates extension of protein folding or onset of disposal

Abstract

The endoplasmic reticulum (ER) is the site of folding for proteins that are resident in the ER or that are destined for the Golgi, endosomes, lysosomes, the plasma membrane, or secretion. Cotranslational addition of preassembled glucose3-mannose9-N-acetylglucosamine2 core oligosaccharides (N-glycosylation) is a common event for polypeptides synthesized in this compartment. Protein-bound oligosaccharides are exposed to several ER glycanases that sequentially remove terminal glucose or mannose residues. Their activity must be tightly regulated because the N-glycan composition determines whether the associated protein is subjected to folding attempts in the ER lumen or whether it is retrotranslocated into the cytosol and degraded.

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Figure 1: The fate of newly synthesized glycoproteins in the ER lumen.
Figure 2: N-glycan processing in the mammalian and yeast ER.
Figure 3: The members of the GH47 family.
Figure 4: Schematic view of degradation kinetics for a model glycoprotein.

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Acknowledgements

M.M. is supported by grants from the Foundation for Research on Neurodegenerative Diseases, Swiss National Center of Competence in Research on Neural Plasticity and Repair, Swiss National Science Foundation, Synapsis Foundation, Bangerter-Rhyner Foundation and Aetas Foundation.

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Molinari, M. N-glycan structure dictates extension of protein folding or onset of disposal. Nat Chem Biol 3, 313–320 (2007). https://doi.org/10.1038/nchembio880

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