Yeast provide a useful model system to study the biosynthesis and processing of
N-and
O-linked glycoprotein glycans. The synthesis of Glc
3Man
9GlcNAc
2-PP-dolichol, initial transfer of the tetradecasaccharides to asparagine residues in nascent proteins, and trimming of the three glucose residues are highly conserved events in yeast and mammalian cells. Whereas mammalian cells generally trim the original oligosaccharide to a trimannosyl core, which in the Golgi apparatus is elongated with varying amounts of GlcNAc, Gal, sialic acid, sulfate and fucose to form multiantennary “complex” glycans, yeast may trim only one mannose from the original oligosaccharide in the endoplasmic reticulum, then elongate the resultant high mannose oligosaccharide in the Golgi to “mannan”, a poly α1, 6-linked mannose backbone with α1, 2-and α1, 3-linked mannose side chains that may consist of 50 to 100 residues. In a significant departure from mammalian cells, where
O-glycosylation of serine/threonine residues occurs wholly in the Golgi, in yeast this event is initiated in the endoplasmic reticulum with the transfer of a single mannose to acceptor amino acids. Subsequently, the
O-linked mannose can be elongated in the yeast Golgi with one to four additional mannose residues. Although yeast and mammalian cells reveal significant differences in the latter stages of
N-and
O-linked glycan processing, the ability to utilize the genetic and biochemical approach in yeast has provided a paradigm for understanding both the specificity and complexity involved in glycoprotein metabolism.
View full abstract