N-linked protein glycosylation in the ER

• N‐linked protein glycosylation in the ER covalently modifies a large number of proteins.
• This modification is catalysed by a single enzyme, oligosaccharyltransferase.
• Oligosaccharyltransferase can modulate the folding of substrate protein, thereby extending its substrate range.

N-linked protein glycosylation in the endoplasmic reticulum (ER) is a conserved two phase process in eukaryotic cells. It involves the assembly of an oligosaccharide on a lipid carrier, dolichylpyrophosphate and the transfer of the oligosaccharide to selected asparagine residues of polypeptides that have entered the lumen of the ER. The assembly of the oligosaccharide (LLO) takes place at the ER membrane and requires the activity of several specific glycosyltransferases. The biosynthesis of the LLO initiates at the cytoplasmic side of the ER membrane and terminates in the lumen where oligosaccharyltransferase (OST) selects N-X-S/T sequons of polypeptide and generates the N-glycosidic linkage between the side chain amide of asparagine and the oligosaccharide. The N-glycosylation pathway in the ER modifies a multitude of proteins at one or more asparagine residues with a unique carbohydrate structure that is used as a signalling molecule in their folding pathway. In a later stage of glycoprotein processing, the same systemic modification is used in the Golgi compartment, but in this process, remodelling of the N-linked glycans in a protein-, cell-type and species specific manner generates the high structural diversity of N-linked glycans observed in eukaryotic organisms. This article summarizes the current knowledge of the N-glycosylation pathway in the ER that results in the covalent attachment of an oligosaccharide to asparagine residues of polypeptide chains and focuses on the model organism Saccharomyces cerevisiae. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.