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. 2018 Apr 20;13(4):833-837.
doi: 10.1021/acschembio.8b00163. Epub 2018 Feb 26.

Biogenesis of Asparagine-Linked Glycoproteins Across Domains of Life-Similarities and Differences

Jerry Eichler  1 , Barbara Imperiali  2
Affiliations

Biogenesis of Asparagine-Linked Glycoproteins Across Domains of Life-Similarities and Differences

Jerry Eichler et al. ACS Chem Biol. .
No abstract available

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Figures

Fig. 1 -
Fig. 1 -. An overview of the components of N-glycosylation across evolution.
Across evolution, N-linked glycans are initially assembled in a stepwise manner on a lipid carrier (step 1). Once assembled, the lipid-linked glycan is translocated across the membrane (step 2) and the glycan moiety is transferred to selected Asn residues of a target protein by the actions of an oligosaccharyl transferase (step 3). At the same time, each component of the N-glycosyation process described above presents domain-specific traits, as described in the different text boxes. For further details on steps 1–3, see Fig. 3. The purple lipid corresponds to phosphorylated dolichol or polyprenol, while the yellow rectangle corresponds to the glycan. The blue entity corresponds to the oligosaccharyl transferase. DolP, dolichol phosphate; DolPP, dolichol diphosphate; OTase, oligosaccharyl transferase; PrenPP, polyprenol diphosphate.
Fig. 2 -
Fig. 2 -. The initial and final steps of N-linked protein glycosylation.
In Eukarya, Bacteria and some Archaea, the N-glycosylation pathway is initiated with polyprenol phosphate phosphoglycosyltransferases (PGTs), which catalyze synthesis of α-linked polyprenol diphosphate-linked sugars. In some Archaea, retaining polyprenol phosphate glycosyltransferases (GTs) mediate synthesis of α-linked polyprenol phosphate-linked sugars. Following glycan assembly, both mono- and diphosphate-linked intermediates serve as substrates for protein N-glycosylation catalyzed by OTases. The sugar drawn in blue corresponds to a hexose or a hexosamine and the mono- and diphosphate linkages are highlighted in yellow.
Fig. 3 -
Fig. 3 -. An overview of the steps involved in N-glycosylation across evolution.
Step 1. Stepwise assembly of lipid-linked glycan. Examples of lipid-linked glycan assembly in each domain are presented. In Homo sapiens (Eukarya), a heptasaccharide is sequentially assembled on DolPP in the ER membrane facing the cytoplasm. Once assembled, the DolPP- heptasaccharide is flipped to face the ER lumen, at which point mannose and glucose moieties are added from the corresponding DolP carriers, which are charged on the cytoplasmic face of the ER membrane and flipped to face the ER lumen, to yield the DolPP-charged tetradecasaccharide. In other Eukarya, simpler DolPP-linked glycans are assembled. In Campylobacter jejuni (Bacteria), a heptasaccharide is assembled onto a polyprenol-PP carrier on the cytoplasmic face of the plasma membrane. In Archaea, considerable variability in seen in terms of glycan composition and the lipid carrier, as exemplified by the N-glycosylation pathways of Haloferax volcanii (top), Methanococcus voltae (middle) and Sulfolobus acidocaldarius (bottom). Where known, the enzymes involved in each step are listed. The identities of the sugars in the three panels are listed in the legend in the bottom right-hand corner. Step 2. Translocation of lipid-linked glycans. Current knowledge of the components and mechanisms involved in translocation of lipid-linked glycans across a membrane in each domain is provided. Step 3. Transfer of glycan to protein. Current knowledge of the transfer of the glycan to target protein Asn residues in each domain is provided.
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