Glycosylation
Glycosylation is the addition of polysaccharides to molecules such as proteins.This process is the first of four principal modification steps in the synthesis of membrane proteins and secretory proteins. The majority of proteins synthesized in the rough ER undergo glycosylation.
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Purpose
The polysaccharide chains attached to the target proteins serve various functions. For instance, some proteins do not fold correctly unless they are glycosylated first. Also, polysaccharides linked at the amide nitrogen of asparagine in the protein confer stability on some secreted glycoproteins. Experiments have shown that glycosylation in this case is not a strict requirement for proper folding, but the unglycosylated protein degrades quickly. Glycosylation may play a role in cell-cell adhesion (a mechanism employed by cells of the immune system) as well.
For N-linked oligosaccharides, a 14-sugar precursor is first added to the asparagine in the polypeptide chain of the target protein. The structure of this precursor is common to most eukaryotes, and contains 3 glucose, 9 mannose, and 2 N-acetylglucosamine molecules. A complex set of reactions attaches this branched chain to a carrier molecule called dolichol, and then it is transferred to the appropriate point on the polypeptide chain as it is translocated into the ER lumen.
The oligosaccharide chain is attached only to asparagine occurring in the tripeptide sequence Asn-X-Ser or Asn-X-Thr, where X is any amino acid, through the action of oligosaccharyl transferase. After attachment, once the protein is correctly folded, the three glucose residues are removed from the chain and the protein is available for export from the ER. The glycoprotein thus formed is then transported to the Golgi where removal of further mannose residues may take place. Mature glycoproteins may contain a variety of oligomannose N-linked oligosaccharides containing between 5 and 9 mannose residues. Further removal of mannose residues leads to a 'core' structure containing 3 mannose, and 2 N-acetylglucosamine residues which may then be elongated witha variety of different monosaccharides including galactose, N-acetylglucosamine, N-acetylgalactosamine, fucose and sialic acid.
Mechanisms
There are various mechanisms for glycosylation, although all share several common features.N-linked glycosylation
N-linked glycosylation of some proteins is required for proper folding.O-linked glycosylation
O-linked glycosylation occurs at a later stage during protein processing, probably in the Golgi apparatus. This is the addition of N-acetyl-galactosamine to Serine or Threonine residues by the enzyme UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase, followed by other carbohydrates (such as galactose and sialic acid).GPI anchor
A special form of glycosylation is the GPI anchor.