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N-Glycosylation Processing Pathways Across Kingdoms Cheng-Yu Chung, Natalia I

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N-Glycosylation Processing Pathways Across Kingdoms Cheng-Yu Chung, Natalia I SnapShot: N-Glycosylation Processing Pathways across Kingdoms Cheng-Yu Chung, Natalia I. Majewska, Qiong Wang, Jackson T. Paul, and Michael J. Betenbaugh Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA Central N-glycosylation processing UDP ALG13 GDP ALG7 ALG14 ALG1 ALG2 ALG11 P P P P P CYTOPLASM P P P P P P GOLGI ER LUMEN GNTI α -Man IA En Bloc ALG3 Transfer ALG9 α-Man IB ER Man I α -Glc I OST ALG10 ALG8 ALG6 ALG12 Asn α -Man IC Asn Asn Asn α -Glc II P P P P P Asn P P P P P ALGs: asparagine-linked N-glycosylation processing enzymes Mammalian Insect Plant Fungi Filamentous fungi α-Man II FUT8 α-1,2-MT XYLT GDP Terminal Asn Asn Asn Asn UDP Asn Galactofuranose GNTII Asn Asn FUT8 f ± α-Gal Asn FUTC3 GNTII High FUT11 α -GALT B14GALTI Och1p Mannose FUT12 glycan α-Man II α-1,2-MT UDP Asn Asn ST3GAL4 Asn Asn GNTIV ST6GAL1 GNTIII GNTV Asn GNase Yeast Hybrid glycan P CMP GNase Asn Asn Tetra- α-Man II Mannosyl- Bisecting antennary phosphate glycan glycan transferase Asn Asn Asn Asn GALT1 Asn ST8SIA2 Core type glycan GNTs B14GALTI α-1,6-MT ST8SIA4 Asn Lewis A structure Polysialylation α-Man PolyLacNAc α-1,2-MT Alternative α-1,3-MT P sialic acid FUT13 ] [ STs Mannosyl- n phosphate Asn Asn Asn transferase Asn Asn Paucimannose Hypermannose glycan Asn Asn Asn glycans Bacteria Archaea Archaea glycan structural diversity Block transfer En Bloc Methanococcus En Bloc Transfer Transfer maripaludis OCH3 Thr OCH AgIB Thr OCH3 3 PERIPLASM PglB B B Asn P - P Asn OSO3 P Asn Asn INNER MEMBRANE P Asn P P Haloferax volcanii Methanococcus fervidus Pgls Flippase P AgIs P P P Flippase P P UDP B Thr CYTOPLASM UDP B UDP Thr Pgls: Protein Asn Asn Methanococcus glycosylation enzymes AgIs : archaeal glycosylation enzymes Pyrococcus furiosus maripaludis Sequential transfer HMW1 Legend Thr Threonine P Phosphate N-acetylglucosamine Asn Asn Asn Glucose Asn Asparagine Dolichol N-acetylneuraminic acid OUTER MEMBRANE HMW1B Mannose Hexuronic Acid Undecaprenol N-glycolylneuraminic acid PERIPLASM Sec Galactose Pentose Pyranose N-acetylgalactosamine INNER MEMBRANE Hexose Rhamnose Xylose N-acetylhexosamine UDP HMWIC Fucose f Galactofuranose B 2,4-diacetamido bacillosamine CYTOPLASM + HMW1 GTase Asn UDP Asn Asn 2,3-diacetamido-2,3-dideoxyglucuronic acid 3-acetamido-2,3-diaminomanuronic acid See online version for 258 Cell 171, September 21, 2017 © 2017 Elsevier Inc. DOI https://doi.org/10.1016/j.cell.2017.09.014 legends and references SnapShot: N-Glycosylation Processing Pathways across Kingdoms Cheng-Yu Chung, Natalia I. Majewska, Qiong Wang, Jackson T. Paul, and Michael J. Betenbaugh Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA N-linked glycosylation in most eukaryotes follows a similar initial processing pathway within the endoplasmic reticulum. The pathway begins with the generation of a lipid- linked oligosaccharide (LLO) by multiple asparagine-linked N-glycosylation processing enzymes (ALG). The oligosaccharide is then transferred “en bloc” onto the polypeptide backbone by oligosaccharyltransferase (OST). Proteins are modified at Asn residues containing the N-X-S/T sequence. Processing then diverges significantly between evolu- tionarily distant species in the Golgi apparatus. Mammalian Processing Pathways —Complex Glycans Containing Galactose and Sialic Acid N-linked glycosylation in humans and other mammals typically results in complex-type glycans, in which two to four branches (or antennae) are extended by adding N-acetyl- glucosamine (GlcNAc) sugars to the outer mannose (Man) residues of the tri-mannosyl core (Man3GlcNAc2). In addition, a “bisecting” GlcNAc can be added to innermost Man residue by one of many GlcNAc transferases (GNTIII) that play a role in generating branches. These antennae are further extended by addition of galactose (Gal) residues via β-1,4 linkages. These branches can be further modified in several ways, including GlcNAc-Gal extensions (LacNAc) or addition of a second Gal residue in some mammals via an α-1,3 linkage, which can elicit an immune response in humans. The β-1,4-linked -Gal residues are then often capped with sialic acid via α-2,3 or α-2,6 linkages. The presence of negatively charged sialic acids, typically either N-acetylneuraminic acid (NANA) or N-glycolylneuraminic acid (NGNA), can play a key role in numerous biological reactions. Multiple sialic acids can sometimes be added via α-2,8 linkages, resulting in polysialylation found on the neural cell adhesion molecule (NCAM) and a few other proteins. Insect Cells—Truncated or Paucimannosidic Glycans and Oligomannosidic Glycans Glycoproteins from insects and insect cells typically yield truncated or paucimannosidic glycans (Man1–3GlcNAc2) or oligomannosidic glycans (Man5–9GlcNAc2) with few if any complex glycans. The existence of these truncated glycans is due to the presence of mannosidases and N-acetylglucosaminidase that trim the Man and GlcNAc residues during N-glycan processing. Another characteristic feature of insect N-linked glycosylation is the presence of up to two core fucose (Fuc) residues, α-1,6-linked and α-1,3-linked, to the innermost GlcNAc. While α-1,6 fucosylation is also common in mammalian species, the α-1,3 linked core Fuc residue can be allergenic or immunogenic to humans. Plants—Hybrid, Paucimannosidic, and Complex-Type Glycans Plants have the capacity to generate hybrid, paucimannosidic, and complex-type N-glycan structures depending on the terminal cellular location of the glycoprotein. Hybrid glycans contain one GlcNAc linked to one of the two outer Man residues of the tri-mannosyl core, with the remaining branch terminating in one or more Man residues. Two sugar residues commonly found in plants, a β-1,2-linked xylose (Xyl) side chain and a core α-1,3-linked Fuc, are involved in plant development but have been found to be immunogenic and allergenic to humans. The most prevalent complex-type N-linked glycosylation pattern found among plant kingdoms is the Lewis-A epitope, which may be associated with plant cell-to-cell communication and plant-pathogen interactions. Lewis-A structures are comprised of an α-1,4-linked fucose attached to the GlcNAc residue of the Galβ-1,3- GlcNAc glycan unit. Fungi—High-Mannose Type Glycan Variants Fungi typically generate variants of high-mannose type N-glycans. However, among fungi, the N-glycans synthesized can differ between yeast and filamentous fungi. Filamen- tous fungi, while frequently generating high-mannose glycans with α-1,6-mannosyltransferases and mannan polymerase complex, do not typically further hyper-mannosylate the structures, although some structures can be capped with galactofuranose. Alternatively, yeast have a unique glycosylation pathway that can lead to hyper-mannosylation with up to 200 Man residues. Bacteria—N-Glycosylation via “En Bloc” or Sequential Transfer One key feature of bacterial glycosylation is the presence of undecaprenyl phosphate (UndP) as the lipid-linked precursor for assembling the LLOs on the cytoplasmic face of the inner membrane, whereas eukaryotes and archaea use dolichol phosphate (DolP) and dolichol pyrophosphate (DolPP) lipid carriers. The model organism for the study of bac- terial N-glycosylation is Campylobacter jejuni (C. jejuni), whose pathway includes the en bloc transfer system. C. jejuni N-glycosylation starts with the formation of a lipid-linked heptasaccharide by several N-linked protein glycosylation enzymes (Pgls). The complete heptasaccharide is then flipped across the inner membrane and into the periplasm by flippase and is finally transferred onto the amino group of the Asn residue of the consensus sequence by the oligosaccharyltransferase, PglB. Distinct from the N-glycosylation en bloc transfer mechanism, “sequential” transfer of sugars to proteins in Haemophilus influenza represents a novel N-linked glycosylation pathway in bacteria. UDP-Gal and UDP-Glc are transferred directly to the N-glycoslyation sequon of high-molecular-weight adhesin 1 (HMW1) by HMW1C enzyme in the cytoplasm, followed by elongation by the same enzyme. HMW1 then crosses the Sec translocation apparatus and is subsequently tethered to the outer-membrane translocation protein HMW1B. Archaea—Diversified Glycosylation Patterns Different from Eukaryotic and Bacterial Counterparts Archaea produce a large variety of N-glycans, often species-specific and differing in size, architecture, and sugar composition. Unlike eukaryotes with a conserved pathway forming the final lipid-linked oligosaccharide (LLO) donor Glu3Man9GlcNAc2-P-P-Dol, Archaea initiate N-glycosylation with a dolichol phosphate containing a shorter lipid length and a higher degree of saturation relative to that of eukaryotes. These lipids are then modified by various Agl (archaeal glycosylation) enzymes to form archaeal LLOs containing different oligosaccharide compositions and structures. The LLO is then flipped across the cytosolic membrane and transferred to an Asn residue by an archaeal oligosaccharide transferase, AlgB, followed by extension reactions in some species. REFERENCES Aebi, M. (2013). Biochim. Biophys. Acta 1833, 2430–2437. Betenbaugh, M.J., Tomiya, N., Narang, S., Hsu, J.T., and Lee, Y.C. (2004). Curr. Opin. Struct. Biol. 14, 601–606. Dean, N. (1999). Biochim. Biophys. Acta 1426, 309–322. Deshpande, N., Wilkins, M.R., Packer, N., and Nevalainen, H. (2008). Glycobiology 18, 626–637. PubMed Eichler, J. (2013). Nat. Rev. Microbiol. 11, 151–156. Jarrell, K.F., Ding, Y., Meyer, B.H., Albers, S.V., Kaminski, L., and Eichler, J. (2014). Microbiol. Mol. Biol. Rev. 78, 304–341. Maras, M., van Die, I., Contreras, R., and van den Hondel, C.A. (1999). Glycoconj. J. 16, 99–107. PubMed Nothaft, H., and Szymanski, C.M. (2010). Nat. Rev. Microbiol. 8, 765–778. Stanley, P., Schachter, H., and Taniguchi, N. (2009). N-Glycans. In Essentials of Glycobiology, Chapter 8, A. Varki, R.D. Cummings, J.D. Esko, H.H. Freeze, P. Stanley, C.R. Bertozzi, G.W.
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