Page last updated: 2024-10-24

protein N-linked glycosylation via asparagine

Definition

Target type: biologicalprocess

The glycosylation of protein via the N4 atom of peptidyl-asparagine forming N4-glycosyl-L-asparagine; the most common form is N-acetylglucosaminyl asparagine; N-acetylgalactosaminyl asparagine and N4 glucosyl asparagine also occur. This modification typically occurs in extracellular peptides with an N-X-(ST) motif. Partial modification has been observed to occur with cysteine, rather than serine or threonine, in the third position; secondary structure features are important, and proline in the second or fourth positions inhibits modification. [GOC:jsg, RESID:AA0151, RESID:AA0420, RESID:AA0421]

N-linked glycosylation is a complex process that involves the attachment of a carbohydrate, known as a glycan, to the amino acid asparagine (Asn) within a protein. This process occurs in the lumen of the endoplasmic reticulum (ER) of eukaryotic cells and is essential for the proper folding, stability, and function of many proteins.

**Steps Involved in N-linked Glycosylation:**

1. **Synthesis of Oligosaccharide Precursor:** In the ER lumen, a branched oligosaccharide precursor is assembled on a lipid carrier called dolichol phosphate. This precursor consists of 14 sugars: two N-acetylglucosamines (GlcNAc), nine mannoses (Man), and three glucoses (Glc).

2. **Transfer to Asparagine Residue:** The oligosaccharide precursor is then transferred en bloc to a specific asparagine residue within a nascent polypeptide chain. This transfer reaction is catalyzed by an enzyme called oligosaccharyltransferase (OST). The recognition sequence for OST is Asn-X-Ser/Thr, where X can be any amino acid except proline.

3. **Processing and Modification:** After transfer, the oligosaccharide undergoes a series of processing and modification steps. These steps include:
* Removal of the three glucose residues by glucosidases.
* Removal of some mannose residues by mannosidases.
* Addition of other sugars, such as fucose, galactose, and sialic acid, by glycosyltransferases.

4. **Quality Control and Folding:** The glycosylation state of a protein can influence its folding and stability. The ER has a quality control system that ensures that only properly folded and glycosylated proteins are transported to the Golgi apparatus.

**Functions of N-linked Glycosylation:**

* **Protein Folding and Stability:** N-linked glycans can enhance protein folding by providing a scaffold for correct protein structure and by shielding hydrophobic regions from the aqueous environment. They can also increase protein stability by reducing aggregation and degradation.

* **Cellular Recognition and Signaling:** Glycans on proteins can serve as recognition signals for other molecules, such as lectins, antibodies, and enzymes. This recognition can be involved in processes like cell-cell adhesion, immune responses, and receptor-ligand interactions.

* **Protein Trafficking and Targeting:** Glycosylation can influence the trafficking and targeting of proteins to specific cellular compartments. For example, certain glycosylation patterns can direct proteins to the lysosome or to the cell surface.

**Disease Relevance:**

Defects in N-linked glycosylation can lead to a variety of diseases, including congenital disorders of glycosylation (CDGs) and certain types of cancer. These disorders can affect the function of various organs and systems in the body.'
"

Proteins (1)

ProteinDefinitionTaxonomy
Beta-galactoside alpha-2,6-sialyltransferase 1A beta-galactoside alpha-2,6-sialyltransferase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P15907]Homo sapiens (human)

Compounds (1)

CompoundDefinitionClassesRoles
cytidine monophosphate n-acetylneuraminic acidCMP-N-acetyl-beta-neuraminic acid : A nucleotide sugar used as a donor by glycosyltransferases for the synthesis of sugar chains

Cytidine Monophosphate N-Acetylneuraminic Acid: A nucleoside monophosphate sugar which donates N-acetylneuraminic acid to the terminal sugar of a ganglioside or glycoprotein.
CMP-N-acyl-beta-neuraminic acidmouse metabolite