Nglykosylation

N-glycosylation, also called N-linked glycosylation, is a co-translational and sometimes post-translational modification in which an oligosaccharide is covalently attached to the amide nitrogen of an asparagine residue within a polypeptide. In eukaryotes, this process occurs in the endoplasmic reticulum and is later remodeled in the Golgi apparatus.

The transfer reaction is catalyzed by the oligosaccharyltransferase (OST) complex, which moves a preassembled dolichol-linked oligosaccharide to the nascent polypeptide at the consensus sequon Asn-X-Ser/Thr (X ≠ Pro). The initial glycan, typically Glc3Man9GlcNAc2, is attached to the growing protein and then processed by ER glucosidases I and II, which trim glucose units and facilitate interactions with the calnexin/calreticulin chaperone system to assist proper folding.

After initial ER processing, N-glycans are further trimmed and elaborated in the Golgi by various glycosidases and glycosyltransferases, producing diverse structures categorized as high-mmannose, complex, or hybrid forms. A key Golgi step involves N-acetylglucosaminyltransferase I (GnTI), which initiates branching necessary for complex and hybrid glycans.

Functions and significance: N-glycans influence protein folding, stability, solubility, trafficking, and interactions, and they participate in quality control and degradation pathways for misfolded proteins. They affect half-life and immunogenic properties of secreted and membrane proteins and are essential for proper maturation of many viral glycoproteins.

Disorders of N-glycosylation, collectively called congenital disorders of glycosylation (CDG), arise from defects in OST components or glycan-processing enzymes and can affect multiple organ systems.