dolichol-linked oligosaccharide biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of dolichol-linked oligosaccharide, usually by a stepwise addition of glycosyl chains to endoplasmic reticulum membrane-bound dolichol-P. [GOC:jl, ISBN:0471331309]

Dolichol-linked oligosaccharide biosynthesis is a crucial process for the assembly of N-linked glycans, which are complex sugar structures attached to proteins. This intricate process takes place in the endoplasmic reticulum (ER) and involves a series of enzymatic reactions.

**1. Synthesis of the Dol-P-P-GlcNAc2 Core Structure:**

* The process begins with the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to dolichol phosphate (Dol-P), catalyzed by GlcNAc-1-phosphate transferase (GPT). This results in the formation of Dol-P-GlcNAc.
* Another molecule of GlcNAc is then transferred from UDP-GlcNAc to Dol-P-GlcNAc, forming Dol-P-P-GlcNAc2. This reaction is catalyzed by GlcNAc transferase I (GlcNAc-TI).

**2. Addition of Mannose Residues:**

* The core structure Dol-P-P-GlcNAc2 is then sequentially glycosylated by the addition of mannose residues from dolichol-phosphate-mannose (Dol-P-Man). This process is facilitated by a series of mannosyltransferases.
* The first mannose is added to Dol-P-P-GlcNAc2 to form Dol-P-P-GlcNAc2-Man, followed by the addition of four more mannose residues, creating Dol-P-P-GlcNAc2-Man5.

**3. Addition of Glucose Residues:**

* Next, two glucose residues are added from dolichol-phosphate-glucose (Dol-P-Glc), catalyzed by glucosyltransferases. The first glucose is added to Dol-P-P-GlcNAc2-Man5, forming Dol-P-P-GlcNAc2-Man5-Glc. Subsequently, the second glucose is added, resulting in Dol-P-P-GlcNAc2-Man5-Glc2.

**4. Transfer to the Protein Substrate:**

* The completed oligosaccharide, Dol-P-P-GlcNAc2-Man5-Glc2, is then transferred from the dolichol carrier to the asparagine residue within a protein substrate in the ER lumen. This reaction is catalyzed by oligosaccharyltransferase (OST).
* During transfer, the two glucose residues are removed by glucosidases, and the mannose residues undergo further modifications, leading to the formation of complex N-linked glycans.

**5. Dolichol Recycling:**

* After the transfer of the oligosaccharide to the protein, the dolichol carrier (Dol-P-P) is recycled back to the ER membrane to participate in further rounds of oligosaccharide biosynthesis.'
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Proteins (2)

Compounds (1)