Oligosaccharyltransferase: the central enzyme of N‐linked protein glycosylation

Abstract

N-linked glycosylation is one of the most abundant modifications of proteins in eukaryotic organisms. In the central reaction of the pathway, oligosaccharyltransferase (OST), a multimeric complex located at the membrane of the endoplasmic reticulum, transfers a preassembled oligosaccharide to selected asparagine residues within the consensus sequence asparagine-X-serine/threonine. Due to the high substrate specificity of OST, alterations in the biosynthesis of the oligosaccharide substrate result in the hypoglycosylation of many different proteins and a multitude of symptoms observed in the family of congenital disorders of glycosylation (CDG) type I. This review covers our knowledge of human OST and describes enzyme composition. The Stt3 subunit of OST harbors the catalytic center of the enzyme, but the function of the other, highly conserved, subunits are less well defined. Some components seem to be involved in the recognition and utilization of glycosylation sites in specific glycoproteins. Indeed, mutations in the subunit paralogs N33/Tusc3 and IAP do not yield the pleiotropic phenotypes typical for CDG type I but specifically result in nonsyndromic mental retardation, suggesting that the oxidoreductase activity of these subunits is required for glycosylation of a subset of proteins essential for brain development.

The atomic structure of a eukaryotic oligosaccharyltransferase complex

“…N-linked glycans serve many essential functions, affecting protein folding and sorting in the endoplasmic reticulum (ER) and mediating interactions of the cell or organism with its environment 4 . Proteins are N-glycosylated in the ER lumen by the oligosaccharyltransferase complex (OST), which transfers a pre-formed 14-sugar oligosaccharide from a dolichol-linked donor to selected asparagine residues within a conserved sequon, NXS/T (where X can be any amino acid but proline) 5,6 .…”

“…Proteins are N-glycosylated in the ER lumen by the oligosaccharyltransferase complex (OST), which transfers a pre-formed 14-sugar oligosaccharide from a dolichol-linked donor to selected asparagine residues within a conserved sequon, NXS/T (where X can be any amino acid but proline) 5,6 . Almost two-third of proteins include the NXS/T sequon and 65–75% of them are glycoproteins 4,7 . Mutations in the OST proteins cause a family of diseases known as congenital disorders of glycosylation 8 .…”

Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p

“…OTase catalyses the key step of N-glycosylation, transfer of oligosaccharide from a dolicholpyrophosphate carrier to asparagines in nascent polypeptides translocated into the ER lumen [16]. OTase is a multiprotein complex consisting of a catalytic subunit, Stt3p, and varying numbers of accessory protein subunits in different organisms [5,17,18].…”

Structure of the mammalian oligosaccharyl-transferase complex in the native ER protein translocon

“…This essential reaction is catalysed by the oligosaccharyl-transferase complex (OST) [1][2][3] , an elaborate multisubunit complex integrated into the endoplasmic reticulum (ER) protein translocon. The catalytic OST subunit is present in two paralogous forms, STT3A and B, joined by at least six accessory subunits of poorly understood function: ribophorin I (RibI), ribophorin II (RibII), OST48, DAD1, N33 or IAP, and OST4.…”