Target type: biologicalprocess
The conversion of N-linked glycan (N = nitrogen) structures from the initially transferred oligosaccharide to a mature form, by the actions of glycosidases and glycosyltransferases. The early processing steps are conserved and play roles in glycoprotein folding and trafficking. [ISBN:0879695595, PMID:12736198]
N-glycan processing is a complex and essential biological process that involves the synthesis, modification, and degradation of N-linked glycans. N-glycans are complex sugar structures attached to asparagine residues of proteins, and they play a crucial role in protein folding, stability, trafficking, and function. The process can be broadly divided into four stages:
1. **Assembly of the precursor oligosaccharide**: The first stage occurs in the endoplasmic reticulum (ER) and involves the assembly of a precursor oligosaccharide, Glc3Man9GlcNAc2, on a lipid carrier called dolichol phosphate. This precursor is assembled stepwise, starting with the transfer of N-acetylglucosamine (GlcNAc) to dolichol phosphate followed by the sequential addition of mannose (Man) and glucose (Glc) residues.
2. **Transfer of the oligosaccharide to the protein**: Once the precursor oligosaccharide is assembled, it is transferred en bloc to an asparagine residue in the protein. This transfer reaction is catalyzed by an enzyme called oligosaccharyltransferase (OST) and requires the consensus sequence Asn-X-Ser/Thr, where X can be any amino acid except proline.
3. **Trimming and processing in the ER**: After the transfer of the oligosaccharide, it undergoes a series of trimming and processing reactions in the ER. The initial three glucose residues are removed by glucosidases I and II, followed by the removal of mannose residues by mannosidases I and II. These trimming reactions ensure that only properly folded proteins are transported out of the ER.
4. **Further processing in the Golgi**: The trimmed oligosaccharide is then transported to the Golgi apparatus, where it undergoes further processing and modifications. In the Golgi, N-glycans are further trimmed by mannosidases and galactosyltransferases, and various sugar residues, such as galactose, N-acetylglucosamine, sialic acid, and fucose, can be added. The specific modifications that occur depend on the type of protein and the cell type.
N-glycan processing is highly regulated and plays a critical role in a wide range of biological processes. For example, N-glycans can:
- **Affect protein folding and stability**: The presence of N-glycans can influence protein folding by providing steric hindrance or by interacting with other proteins.
- **Regulate protein trafficking**: N-glycans can act as signals that direct proteins to their correct cellular destinations.
- **Modulate protein-protein interactions**: N-glycans can participate in protein-protein interactions, affecting the formation of complexes.
- **Influence protein function**: N-glycans can affect enzyme activity, receptor binding, and immune responses.
Defects in N-glycan processing can lead to various diseases, including congenital disorders of glycosylation (CDGs), which are characterized by a broad spectrum of clinical symptoms due to impaired protein function. Understanding N-glycan processing is essential for comprehending the diverse roles of glycosylation in biology and for developing new therapeutic strategies targeting glycosylation pathways.'
"
Protein | Definition | Taxonomy |
---|---|---|
Alpha-mannosidase 2 | An alpha-mannosidase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16706] | Homo sapiens (human) |
Neutral alpha-glucosidase C | A neutral alpha-glucosidase C that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8TET4] | Homo sapiens (human) |
Neutral alpha-glucosidase AB | A neutral alpha-glucosidase AB that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14697] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
cisapride | cisapride : The amide resulting from formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-amine. It has been used (as its monohydrate or as its tartrate) for the treatment of gastro-oesophageal reflux disease and for non-ulcer dyspepsia, but its propensity to cause cardiac arrhythmias resulted in its complete withdrawal from many countries, including the U.K., and restrictions on its use elsewhere. Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed) | benzamides | |
1-deoxynojirimycin | 1-deoxy-nojirimycin: structure in first source duvoglustat : An optically active form of 2-(hydroxymethyl)piperidine-3,4,5-triol having 2R,3R,4R,5S-configuration. | 2-(hydroxymethyl)piperidine-3,4,5-triol; piperidine alkaloid | anti-HIV agent; anti-obesity agent; bacterial metabolite; EC 3.2.1.20 (alpha-glucosidase) inhibitor; hepatoprotective agent; hypoglycemic agent; plant metabolite |
labetalol hydrochloride | salicylamides | ||
homonojirimycin | homonojirimycin: inhibits alpha-glucosidase; RN given for (2R-(2alpha,3alpha,4beta,5alpha,6beta))-isomer; structure in first source | ||
1,4-dideoxy-1,4-iminoarabinitol, (2r-(2alpha,3beta,4beta))-isomer | pyrrolidines |