Protein glycosylation is a ubiquitous and complex post-translational modification of proteins. It plays an important role in organisms, participating in the regulation of important biological processes such as cell recognition, adhesion, and signal transduction. Glycosylation is mainly divided into two categories: N-glycosylation and O-glycosylation, according to the difference of connecting amino acid residues. Humans have more than 7000 proteins modified by N-glycosylation. The N-glycosylation process is dependent on the formation of dolichol phosphate glycan (Dol-P-Glc3Man9GlcNAc2). After the Dol-P-glycan structure is completed, oligosaccharyltransferase (OST) transfers the glycan to the asparagine (Asn) residue in the consensus sequence N-X-S/T of nascent protein. Afterward, glycan protein is further modified and processed in the endoplasmic reticulum (ER) and Golgi apparatus. In these processes, most steps are tightly controlled by Glycosyltransferases and glycosidases encoded by different genes.
Fig.1 N-Glycan biosynthesis in the secretory pathway. (Reily, et al., 2019)
N-Glycosylation is required for survival in all eukaryotes. N-Glycosylation Modification plays an important role in the correct folding, functional localization, and intracellular transport of proteins, participating in many important life processes such as signal transduction, cell adhesion, and cell-cell interaction. Important molecules in the immune system such as immunoglobulin A (IgA), IgD, IgE, IgG, IgM, etc. are all glycoproteins. Among them, IgG is one of the most deeply studied proteins, and its glycosylation modification will change under different physiological and pathological conditions. Furthermore, N-glycan structures are involved in the development and exacerbation of diseases. Therefore, it is very important to understand the biosynthetic pathway of N-glycans and to elucidate the mechanism of action of N-glycan structures in cells.
Disorders of protein N-glycosylation are caused by deficiencies of glycosylation enzymes or transporters. Congenital defects in glycosyltransferases and glycosidases caused by specific mutations lead to the development of rare, but serious disease-Congenital Disorders of Glycosylation (CDG). Therefore, Glycan Analysis is a method used to detect CDG in laboratories. Here we describe the CDG induced by disorders of primarily N-linked monosaccharide synthesis and interconversion and disorders of N-linked glycosylation.
The biosynthesis of N-glycans in eukaryotes starts from Dol-P in the ER. Afterward, N-acetylglucosamine (GlcNAc), mannose (Man), and glucose (Glc) were transferred onto Dol-P from uridine diphosphate (UDP)-GlcNAc, guanosine diphosphate (GDP)- Man, GDP-Man, Dol-P-Man, and Dol-P-glucose. Here, we focus on defects in the synthesis and interconversion of primarily N-linked monosaccharides, such as phosphomannomutase-2 (PMM2) and mannose-phosphate isomerase (MPI).
N-Linked glycosylation mainly involves three steps: the biosynthesis of N-glycan precursors in the ER, the overall transfer of N-glycans, and the processing of N-glycans. Defects in N-linked glycosylation that are aberrantly initiated by glycosidases and glycosyltransferases are described.
CD BioGlyco has specialized in the research of glycosylation for many years and has developed first-class Glycomics and Glycoproteomics platforms. We are pleased to share our knowledge and experience in the field of glycosylation. If you are interested in our services, please feel free to contact us for more information.
Reference:
