N-Glycanase

Related Reading

N-glycanases are enzymes in the cytoplasmic matrix responsible for the excision of asparagine-linked oligosaccharide chains in misfolded glycoproteins. The action of the enzyme contributes to the subsequent degradation of the protein. Glycan chains, which serve as cofactors for summarized proteins, generally have fewer than 15 monosaccharides and are therefore also called oligosaccharide chains. The structure of oligosaccharide chains is very diverse and its comparable to nucleic acids and proteins. Glycoconjugates are chains of various sugars linked in human cells and are components of glycolipids and glycoproteins. In cellular tissue structure, oligosaccharides are a cellular structural organization attached to and rooted between cellular proteins, which are distributed on cell membranes and serve to conduct information in cell life, and because their complex structure changes with the environment, their function is very similar to that of the human nervous tissue. These oligosaccharide chains are also involved in the adhesion between cells, as receptors for pathogenic bacteria and toxins and for hormones, enzymes antibodies and lectins.

Structure

The catalytic residues of cytoplasmic PNGase is located in a structural domain called the transglutaminase structural domain. In contrast to the yeast direct homologs, N-glycanases have extended N-terminal and C-terminal sequences in addition to the transglutaminase structural domain. Among the other domains found in N-glycanases, the PUB (PNGase and ubiquitin-related) domain was first identified by bioinformatics analysis. Although it was initially assumed that it might act as a protein-protein interaction domain, experimental evidence supporting this hypothesis is now accumulating. On the other hand, the C-terminal PAW structural domain (a structural domain present in PNGases and other worm proteins) has now been shown to be involved in the binding of oligosaccharides to PNGase.

Role of N-Glycanase in MHC class I-mediated antigen presentation

Although the biological significance of N-Glycanase-mediated in vivo deglycosylation is not yet fully understood, it has been well documented to play a key role in MHC class I-mediated antigen presentation. First, when natural peptide targets of melanoma-reactive cytotoxic T cell clones were examined, Asn residues at potential N-glycosylation sites were found to be converted to Asp in peptides derived from tyrosinase, a key enzyme for melanogenesis. These results raise the possibility that N-Glycanase may be the enzyme responsible for this Asn to Asp conversion. In order to present the tyrosinase-derived peptide efficiently to MHC class I molecules, it was suggested that tyrosinase was first transferred to ER to receive the N-glycan. Subsequently, it was found that unglycosylated tyrosinase is rapidly degraded and therefore cannot be efficiently presented to MHC class I molecules. N-Glycanase activity was also shown to affect the efficiency of antigen presentation, pointing to the functional importance of N-Glycanase-mediated deglycosylation in antigenic peptide processing. N-Glycanase-mediated (N-glycosylation-)Asn-to-Asp deamidation N-Glycanase-mediated (N-glycosylation-) Asn-to-Asp deamidation and other reactions such as transpeptidation constitute unconventional post-translational modifications of antigenic peptides presented by MHC class I molecules.

Conclusion

N-Glycanase is a des-N glycosylase that is widely expressed in mammalian organs and tissues, and this protein is also evolutionarily conserved throughout eukaryotes. However, much remains to be clarified as far as the mystery about this enzyme is concerned. For example, the immediate homologue of the N-Glycanase gene of P. vulgaris (PNG1) encodes the catalytically inactivated protein as an enzyme due to an intrinsic mutation in the catalytic residue, but strains bearing the mutation exhibit severe temperature sensitivity defects in polar growth. These results clearly indicate that, at least for the fungal direct homologs, N-Glycanase -direct homologs have enzyme-independent functions.