Lipid-linked oligosaccharide biosynthesis (Saccharomyces cerevisiae)

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In eukaryotes, N-linked (asparagine-linked) glycosylation is the most common form of protein modification of secretory and membrane proteins, and is involved in a variety of cellular processes, such as protein folding, sorting and stability (reviewed in (CITS: [15189166][8472892][3896128])). The initial steps of N-linked glycosylation, which are also known as the dolichol pathway of N-linked glycosylation, and lipid- and dolichol-linked oligosaccharide biosynthesis, involve the synthesis of a core oligosaccharide (glucosyl)₃(mannosyl)₉(N-acetylglucosamine)₂, abbreviated, Glc₃Man₉GlcNAc₂, on the lipid carrier, dolichol-pyrophosphate (Dol-PP) (reviewed in (CITS: [9878760][8472892][3896128])). The ordered assembly of the core oligosaccharide is highly conserved throughout eukaryotic evolution. The assembly starts on the cytoplasmic side of the endoplasmic reticulum (ER), where N-acetylglucosamine-1-phosphate (GlcNAc-1-phosphate) is transferred from uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) to dolichol-phosphate (Dol-P) followed by the addition of one N-acetylglucosamine (GlcNAc) and five mannose residues from UDP-GlcNAc and guanosine 5'-diphosphomannose (GDP-Man), respectively. The resulting lipid-linked precursor (Man₅GlcNAc₂-PP-Dol) is translocated "flipped" into the lumen of the ER by a flippase, which which is endoded by RFT1 in S. cerevisiae. Once in the lumen, the oligosaccharide is extended by four mannose and three glucose residues derived from dolichyl-phosphate-mannose (Dol-P-Man) and dolichyl-phosphate-glucose (Dol-P-Glc), respectively. The enzyme complex oligosaccharyltransferase (OST) transfers the preassembled oligosaccharide, Glc₃Man₉GlcNAc₂, from the lipid carrier Dol-PP to selected asparagine residues of nascent polypeptides as the polypeptides pass into the lumen of the ER (CITS: [11580295])(CITS: [9405463]). Once attached to the protein, the N-linked oligosaccharide is further modified by a series of trimming and elongation reactions beginning in the ER and ending in the late Golgi compartment (CITS: [8054711]). In the ER, the oligosaccharide is trimmed of its 3 glucose residues and a specific mannose residue to form Man₈GlcNAc₂. The glucose residues are removed by glucosidases I and II, and in S. cerevisiae the mannose is removed by the alpha-1,2-mannosidase Mns1p, which is part of the editing mechanism that promotes the exit of correctly folded glycoproteins from the ER (CITS: [9732283]). Once the four monosaccharides are removed, the glycoproteins are transported from the ER to the Golgi, where the yeast and mammalian pathways diverge (CITS: [3304149]). The lipid-linked oligosaccharide biosynthetic pathway is of particular interest in humans, because defects in the glycosyltransferases involved lead to congenital disorders of glycosylation (CITS: [11306275][17024709]). SOURCE: SGD pathways, http://pathway.yeastgenome.org/server.html

GenMAPP remarks 

Based on http://pathway.yeastgenome.org/biocyc/