Structure of glycans. The lettering (a–n) follows the order of addition of monosaccharides in the synthesis of Glc₃Man₉GlcNAc₂-P-P-dolichol. GI removes residue n, and GII removes residues l and m. GT adds residue l to residue g. M8A lacks residues g and l–n; M8B formed by mammalian or yeast cell ER α-mannosidase I lacks residues i and l–n; and Man₈GlcNAc₂ isomer C lacks residues k and l–n. The smallest glycan formed in the S. pombe ER (Man₇GlcNAc₂) lacks residues i, k, and l–n.

Model proposed for the quality control of glycoprotein folding. Proteins entering the ER are N-glycosylated by the oligosaccharyltransferase (OST) as they emerge from the translocon. Two glucoses are removed by the sequential action of GI and GII to generate monoglucosylated species that are recognized by CNX and/or CRT (only CNX is shown), which is associated with ERp57. The complex between the lectins and folding intermediates/misfolded glycoproteins dissociates upon removal of the last glucose by GII and is reformed by GT activity. Once glycoproteins have acquired their native conformations, either free or complexed with the lectins, GII hydrolyzes the remaining glucose residue and releases the glycoproteins from the lectin anchors. These species are not recognized by GT and are transported to the Golgi. Glycoproteins remaining in misfolded conformations are retrotranslocated to the cytosol, where they are deglycosylated and degraded by the proteasome. One or more mannose residues may be removed during the whole folding process.