Biosynthesis of N-linked glycoproteins

This process occurs in the ER and can be continued in the GA.

  1. First a lipid-linked oligosaccharide precursor is synthesized. Its structure is the same in animals, plants and single-celled eucaryotes :

    The precursor oligosaccharide is linked by a pyrophosphoryl group to dolichol. It is a long (75-95 carbon atoms), highly hydrophobic polyisoprenoid lipid :

    Dolichol is long enough to span the membrane 4 - 5 times. It is localized on the rough ER. The biosynthesis starts at the cytosolic face of the ER. At the beginning 2 GlcNAc and 5 mannose residues are added one at time to dolichol phosphate. Then the dolichol pyrophosphoryl oligosaccharide is flipped to the luminal face. In the latter reactions each mannose or glucose residue is transferred from nucleotide sugar to dolichol on the cytosolic face of the ER. Then it is flipped and transferred to the growing oligosaccharide. The carrier is then flipped back again to the cytosolic face.

  2. The oligosaccharide precursor is transferred from the dolichol to an Asn residue on the nascent polypeptide. Thus the glycosylation occurs cotranslationally. The Asn residue must be in a sequence N-X-S/T where X cannot be Pro or Asp.
    The process is catalyzed by oligosaccharide protein transferase. The enzyme is built up of three subunits. Two of them are ribophorins - ER transmembrane proteins. Their cytosolic parts bind to the larger subunit of the ribosome (they act as an anchor). The third subunit has the catalytic activity.

Modifications of N-linked oligosaccharides

There are two main processing pathways :

For lysosomal enzymes

For non-lysosomal glycoproteins

Go to :

Biosynthesis of GPI-membrane anchors

Biosynthesis of glycoproteins