Difference Between N Glycosylation and O Glycosylation

The key difference between N glycosylation and O glycosylation is that N glycosylation occurs in asparagine residues whereas O glycosylation occurs in the side chain of serine or threonine residues.

Glycosylation is the controlled enzymatic modification of an organic molecule such as a protein via the addition of a sugar molecule. It is an important biochemical process and a highly regulated mechanism of secondary protein processing within cells.

CONTENTS

1. Overview and Key Difference
2. What is N Glycosylation 
3. What is O Glycosylation
4. Side by Side Comparison – N Glycosylation vs  O Glycosylation in Tabular Form
5. Summary

What is N Glycosylation?

N glycosylation or N-linked glycosylation is the attachment of an oligosaccharide sugar molecule to a nitrogen atom in the asparagine residue of a protein molecule. This sugar molecule is also named as glycan. It is attached to the nitrogen atom in the amide group of the asparagine residue. Further, this linking process is important in both the structure and function of some eukaryotic proteins. Moreover, this process takes place in eukaryotes, widely in archaea, and rarely in bacteria.

The attachment of a glycan residue to a protein requires the recognition of a consensus sequence. For example, N-linked glycans are almost always attached to the nitrogen atom of an asparagine side chain that occurs as a part of Asn-X-Ser/Thr consensus sequence. Here, X is any amino acid except proline (Pro). The N-linked glycans have both intrinsic and extrinsic functions.

There are important clinical applications of N glycosylation process. For example, it is associated with different diseases, including rheumatoid arthritis, type 1 diabetes, Crohn’s disease, and cancers. Moreover, many therapeutic proteins in the market are antibodies that are N-linked glycoproteins.

What is O Glycosylation?

O glycosylation or O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine or threonine residues in a protein molecule. This process is a post-transitional modification that happens after the synthesis of the protein. This process can take place in both eukaryotes and prokaryotes. E.g. in eukaryotes, N glycosylation occurs in the endoplasmic reticulum, Golgi apparatus and sometimes in the cytoplasm while in prokaryotes, it occurs in the cytoplasm.

During O glycosylation process, several sugars can be added to the serine or threonine, and this addition can affect the protein in different ways via changing the protein stability and by regulating the protein activity.

What is the Difference Between N Glycosylation and O Glycosylation?

N glycosylation and O glycosylation are important biochemical processes. The key difference between N glycosylation and O glycosylation is that the N glycosylation occurs in asparagine residues whereas the O glycosylation occurs in the side chain of serine or threonine residues. Mainly, N glycosylation occurs in eukaryotic organisms and in archaea while O glycosylation occurs only in prokaryotic organisms.

Below is a summary tabulation of the difference between N glycosylation and O glycosylation.

Summary – N Glycosylation vs O Glycosylation

In brief, N glycosylation or N-linked glycosylation is the attachment of an oligosaccharide sugar molecule to a nitrogen atom in the asparagine residue of a protein molecule. O glycosylation or O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine or threonine residues in a protein molecule. Therefore, the key difference between N glycosylation and O glycosylation is that N glycosylation occurs in asparagine residues, whereas O glycosylation occurs in the side chain of either serine or threonine residues.

Reference:

1. “Linked Glycosylation.” Science Direct. Available here.

Image Courtesy:

1. “Types of glycans” By Dna 621 – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Common O-glycans found on alpha-dystroglycan” By Waffeln – Own work (CC BY-SA 4.0) via Commons Wikimedia