Glycosylation is a crucial post-translational modification that regulates the structure and function of proteins. It involves the attachment of glycans to specific amino acid residues on the protein via enzymatic reactions. The glycan structures vary depending on the type of glycosylation and the organism, tissue, and cell type in which it occurs. In this article, we will delve into the different types of glycosylation and their modification mechanisms.
O-glycosylation is a type of glycosylation that occurs on serine or threonine residues adjacent to proline. There is no specific glycosylation sequence identified yet for O-glycosylation. The glycan structures formed by O-glycosylation are mostly oligosaccharides that gradually add monosaccharides, and some cases only add one monosaccharide. The glycan formed by O-glycosylation does not have a sugar base and has a single main bone with one or no branch.
N-glycosylation is a type of glycosylation that occurs on the amide nitrogen of the asparagine side chain. In animal cells, almost all such glycosylation modifications are GlcNAc, and all are in β configuration. The amino acid sequence for N-glycosylation is Asn-Xaa-Ser/Thr/Cys, where Xaa can be any amino acid except Pro. The glycan formed by N-glycosylation has a sugar base and multiple branches.
C-glycosylation is a rare type of glycosylation in which a molecule of mannose is connected to the C of the 2nd position of the tryptophan indole ring via a C-C bond. It mainly occurs in the first tryptophan residue of W-X-X-W-W-X-X-C or W-X-X-F.
Glycosylation is essential for many physiological processes, such as cellular immunity and protein translation regulation, protein degradation, and many other biological processes. It also plays a significant role in the development of various diseases. Abnormal glycosylation is associated with many diseases, such as type II diabetes, where hyperglycemia leads to abnormal modification of O-GlcNAc, reducing the sensitivity of cells to signals and preventing insulin from using large amounts of glucose.
Inhibitors for glycosylation, such as α-glucosidase, N-butyl-1-deoxynojirimycin, and O-butyl-1-deoxynojirimycin, have been used in disease treatment research. For instance, α-glucosidase is used in clinical trials for diabetes, while N-butyl-1-deoxynojirimycin and O-butyl-1-deoxynojirimycin are used in clinical trials for HIV.
In conclusion, glycosylation is a vital post-translational modification that is crucial for regulating the structure and function of proteins. It occurs in many important proteins involved in physiological processes and plays a significant role in the development of various diseases. The different types of glycosylation have unique modification mechanisms, and inhibitors for glycosylation are being used in disease treatment research.
