N-linked glycosylation is an important post-translational modification for eukaryotic proteins in the secretory pathway. These account for almost half of all known proteins and include most membrane proteins like receptors and innate immunity proteins, secreted proteins like immunoglobulins, clotting factors, and hormones, and most of the proteins inside the endoplasmic reticulum and its surface. The first part of N-linked glycosylation is the synthesis of a lipid-linked oligosaccharide composed of 14 sugars (referred to as LLO or N-glycan precursor). This is one of the best-conserved eukaryotic biosynthetic pathways. The LLO is then transferred co-translationally to a nascent protein, forming an N4-glycosyl link to an asparagine residue within the consensus sequence asparagine - X - threonine by the oligosaccharyl transferase (OST) enzyme complex. This glycosylation is required for the folding of the majority of the proteins in the endoplasmic reticulum. After its transfer to the nascent protein, initial modifications of the glycan moiety regulate the correct folding of the glycoprotein. If folding succeeds, the N-glycan can undergo a very complex set of modifications, best represented as a network. This process is not well understood yet, but is known to generate millions of different glycan structures, regulating the properties of the glycoproteins to which they are attached. Most of the genes in the N-glycosylation pathway are highly conserved in eukaryotes. Mutations in them are associated with a diverse group of disorders collectively known as Congenital Disorders of Glycosylation (type I and II) (Sparks and Krasnewich 2009). Understanding the molecular mechanisms of glycosylation is also important for the design of drugs aimed at targets such as viral capsid glycoproteins, and fungal glycosylation systems (which are slightly different from the human one) (Stanley P et al, 2009).
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