Handbook of Glycosyltransferases and Related Genes pp 1239-1247 | Cite as
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).
KeywordsCytoplasmic Face Nascent Protein Sugar Donor Cytosolic Face GlcNAc Transferase
- Absmanner B, Schmeiser V, Kampf M, Lehle L (2010) Biochemical characterization, membrane association and identification of amino acids essential for the function of Alg11 from Saccharomyces cerevisiae, an alpha1,2-mannosyltransferase catalysing two sequential glycosylation steps in the formation of the lipid-linked core oligosaccharide. Biochem J 426:205–217PubMedCrossRefGoogle Scholar
- Kampf M, Absmanner B, Schwarz M, Lehle L (2009) Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional alpha1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis. J Biol Chem 284:11900–11912PubMedCrossRefGoogle Scholar
- Rind N, Schmeiser V, Thiel C, Absmanner B, Lübbehusen J, Hocks J, Apeshiotis N, Wilichowski E, Lehle L, Körner C (2010) A severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation-Ip. Hum Mol Genet 19(8):1413–24PubMedCrossRefGoogle Scholar
- Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschutter A, von Figura K, Lehle L, Korner C (2003) A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis. J Biol Chem 278:22498–22505PubMedCrossRefGoogle Scholar