Alg1, Alg2, and Alg11 mannosyltransferases of the endoplasmic reticulum

Asparagine (N)-linked glycans are common posttranslational modifications found on many glycoproteins in bacteria to man. These glycans are not produced by addition of individual sugars directly on an Asn residue side chain of a protein, but rather as lipid-linked precursors that only after their assembly are transferred to nascent proteins. Once attached to protein, these glycans are modified in a variety of different ways. The structures of mature protein N-linked glycans vary enormously among eukaryotic species and even among cells of the same species. This is in stark contrast to the highly conserved structure of the preassembled lipid-linked precursor Glc₃Man₉GlcNAc₂ oligosaccharide (LLO), which, with few exceptions, is shared by all eukaryotes (Fig. 110.1). The conserved structure of the LLO is a reflection of the evolutionary conservation of the 12 different glycosyltransferases that catalyze its production. LLO synthesis begins on the cytoplasmic face of the endoplasmic reticulum and is completed in the lumen (Fig. 110.2). Two N-acetyl-glucosamines (GlcNAc) and five mannoses (man) are covalently attached to dolichol pyrophosphate (PP-Dol) on the cytosolic face of the ER. After flipping across the membrane, seven sugars (four man and three glucoses (glc)) are attached in the lumen and then transferred to nascent proteins by oligosaccharyltransferase (Fig. 110.2).