N-linked glycosylation

The different types of glycans produced in different organisms.

N-linked glycosylation, is the attachment of the sugar molecule oligosaccharide known as glycan to a nitrogen atom (the amide nitrogen of an asparagine (Asn) residue of a protein), in a process called N-glycosylation, studied in biochemistry.[1] This type of linkage is important for both the structure[2] and function[3] of some eukaryotic proteins. The N-linked glycosylation process occurs in eukaryotes and widely in archaea, but very rarely in bacteria. The nature of N-linked glycans attached to a glycoprotein is determined by the protein and the cell in which it is expressed.[4] It also varies across species. Different species synthesize different types of N-linked glycan.

Energetics of bond formation

There are two types of bonds involved in a glycoprotein: bonds between the saccharides residues in the glycan and the linkage between the glycan chain and the protein molecule.

The sugar moieties are linked to one another in the glycan chain via glycosidic bonds. These bonds are typically formed between carbons 1 and 4 of the sugar molecules. The formation of glycosidic bond is energetically unfavourable, therefore the reaction is coupled to the hydrolysis of two ATP molecules.[4]

On the other hand, the attachment of a glycan residue to a protein requires the recognition of a consensus sequence. N-linked glycans are almost always attached to the nitrogen atom of an asparagine (Asn) side chain that is present as a part of Asn–X–Ser/Thr consensus sequence, where X is any amino acid except proline (Pro).[4]

In animal cells, the glycan attached to the asparagine is almost inevitably N-acetylglucosamine (GlcNAc) in the β-configuration.[4] This β-linkage is similar to glycosidic bond between the sugar moieties in the glycan structure as described above. Instead of being attached to a sugar hydroxyl group, the anomeric carbon atom is attached to an amide nitrogen. The energy required for this linkage comes from the hydrolysis of a pyrophosphate molecule.[4]

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