The glycosylation of proteins (Test)

The glycosylation of proteins (Test)

Structures of glycans

Glycosylation is a post translational modification (PTM) in which complex polysaccharide molecules are covalently bonded to proteins or lipids. The process of glycosylation principally takes place in the endoplasmic reticulum (ER) and the Golgi apparatus (GA), and it is mediated by glycotransferases and glycosidases enzymes that respectively attach and remove specific sugar residues. Glycans display an important structural heterogeneity due to their monosaccharide composition and the different type of glycosidic bonds that links them together. The same glycosylation site does not necessary harbour the same glycan structure, leading to different protein glycoforms.

The main classes of glycans includes:

  • The N-glycans are attached to an asparagine (N) residue within the consensus N-X-S/T sequence of a protein. They are characterized by a conserved core made of 2 GlcNAc and 3 mannose residues. The process of N-glycosylation involves the assembly of a large high mannose glycan precursor and its attachment to the protein in the ER. The precursor is further enzymatically trimmed and maturated into a complex or hybrid glycan class during its way through the Golgi apparatus. The N-glycans are usually classified into high mannose, hybrid, complex or bisected categories.
  • The O-glycans are attached to a threonine or a serine residue of a protein without a known recognition of a consensus sequence. O-glycans are built on several possible initial core structures that can be extended by addition of other sugar residues by different glycosyltransferases. The resulting O-glycans can be linear or branched leading to complex and variated structures.
  • The glycolipids are a class of lipids that contains sugar residues attached to the lipid moiety. Glycolipids are anchored into the cellular membranes by sphingosine or glycerol based fatty acid chains. The glycan moity is composed from one to several sugar residues and usually exposed to the extracellular medium. Glycosphingolipids tends to be found in animal reign whereas the glycoglycerolipids are most associated with plants and bacteria cells.

Biological and economical importance of glycosylation of proteins and lipids

Glycosylation of proteins modification plays a critical role in protein folding, stability, trafficking, and affect their biological functions. Glycolipids play a role in the stability of the cell membrane and in cell interactions (e.g. blood types).

Glycans act as identification tags that allow cells to recognise each other for biological processes like immune response, tissue development, and cell adhesion.

Glycan biological functions are also exploited by pathogens as they modulate the infectivity, tropism and immunogenicity of virions (e.g. lentivirus and coronavirus).

There is a specificity in the glycosylation profile between plants, insects, animals or fungi cells. This differentiation can go down to the species level with for instance the absence of endogenous N-glycolylneuraminic acid in human tissues or galactose-α-1,3-galactose epitope in human and some monkeys. The presence of exogenous of glycan types can have a major impact on the safety of recombinantly produced therapeutics proteins and in-depth characterization of protein carbohydrates is required by health administrations before marketing authorization. Glycan structures and compositions can also affect the drug’s efficacy, stability, and immunogenicity. A better understanding and intentional modifications of glycan structures can even be an option to optimize the pharmacokinetics and the therapeutic activity of drug’s proteins.