N-Linked Protein Glycosylation in the Endoplasmic Reticulum
Open accessAbstract
The attachment of glycans to asparagine residues of proteins is an abundant and highly conserved essential modification in eukaryotes. The N-glycosylation process includes two principal phases: the assembly of a lipid-linked oligosaccharide (LLO) and the transfer of the oligosaccharide to selected asparagine residues of polypeptide chains. Biosynthesis of the LLO takes place at both sides of the endoplasmic reticulum (ER) membrane and it involves a series of specific glycosyltransferases that catalyze the assembly of the branched oligosaccharide in a highly defined way. Oligosaccharyltransferase (OST) selects the Asn-X-Ser/Thr consensus sequence on polypeptide chains and generates the N-glycosidic linkage between the side-chain amide of asparagine and the oligosaccharide. This ER-localized pathway results in a systemic modification of the proteome, the basis for the Golgi-catalyzed modification of the N-linked glycans, generating the large diversity of N-glycoproteome in eukaryotic cells. This article focuses on the processes in the ER. Based on the highly conserved nature of this pathway we concentrate on the mechanisms in the eukaryotic model organism Saccharomyces cerevisiae.
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The oligosaccharide-transferase complex transfers 14 component sugars composed of glucose and mannose from dolichol to nascent chain asparagines to complete N-linked glycosylation, which is essential for folding secreted and plasma membrane-linked proteins and mediated through glucose- and mannose-derived glycans.
“This complex transfers 14 component sugars composed of glucose and mannose from dolichol to nascent chain asparagines to complete N-linked glycosylation, which is essential for folding secreted and plasma membrane-linked proteins and mediated through glucose- and mannose-derived glycans.53”
From 2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer’s resilience (2023) · cites this paper as [53]
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Roles of N-Linked Glycans in the Endoplasmic Reticulum
Helenius, A., & Aebi, M. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073752 · Cited by 2,037 · see citing works
Self-citationCantagrel, V., Lefeber, D. J., Ng, B. G., Guan, Z., Silhavy, J. L., Bielas, S. L., Lehle, L., Hombauer, H., Adamowicz, M., Swiezewska, E., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.001 · Cited by 309 · see citing works
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Mechanisms Controlling PD-L1 Expression in Cancer
Cha, J., Chan, L.-C., Li, C., Hsu, J. L., & Hung, M. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.030 · Cited by 1,054 · see citing works
“N-linked glycosylation of PD-L1 Glycosylation is the most abundant PTM found in one-third of all proteins in mammals (Breitling and Aebi, 2013).”
BackgroundRegulatory mechanisms of PD-1/PD-L1 in cancers
Lin, X., Kang, K., Chen, P., Zeng, Z., Li, G., Xiong, W., Yi, M., & Xiang, B. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02023-w · Cited by 850 · see citing works
“Glycosylation is a major post-translational modification that is important for protein folding, localization, intra-cellular transport, and immunogenicity [275].”
Background2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy
Zhang, D., Li, J., Wang, F., Hu, J. X., Wang, S., & Sun, Y. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.09.003 · Cited by 464 · see citing works
STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion
Hsu, J.-M., Xia, W., Hsu, Y.-H., Chan, L.-C., Yu, W.-H., Cha, J., Chen, C., Liao, H.-W., Kuo, C., Khoo, K., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04313-6 · Cited by 437 · see citing works
Glycosylation-directed quality control of protein folding
Xu, C., & Ng, D. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4073 · Cited by 410 · see citing works
Duan, L., Zheng, Q., Zhang, H., Niu, Y., Lou, Y., & Wang, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.576622 · Cited by 403 · see citing works
“The unprocessed precursor harbors an endoplasmic reticulum (ER) signal sequence located at the N terminus, which targets the S glycoprotein to the RER membrane and is removed by cellular signal peptidases in the lumen of the ER (14, 15).”
BackgroundIL-6/JAK1 pathway drives PD-L1 Y112 phosphorylation to promote cancer immune evasion.
Chan, L.-C., Li, C.-W., Xia, W., Hsu, J.-M., Lee, H.-H., Cha, J.-H., Wang, H.-L., Yang, W.-H., Yen, E.-Y., Chang, W.-C., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126022 · Cited by 332 · see citing works
Carboxylesterases in lipid metabolism: from mouse to human
Lian, J., Nelson, R., & Lehner, R. S. (2017) · Protein & Cell · doi:10.1007/s13238-017-0437-z · Cited by 306 · see citing works
“The formation of disulfide bond and N-linked glycosylation are processes that occur in the ER lumen (Bulleid, 2012; Breitling and Aebi 2013).”
BackgroundA palette of fluorescent proteins optimized for diverse cellular environments
Costantini, L. M., Baloban, M., Markwardt, M. L., Rizzo, M. A., Guo, F., Verkhusha, V. V., & Snapp, E. L. (2015) · Nature Communications · doi:10.1038/ncomms8670 · Cited by 264 · see citing works
Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy
Hsu, J.-M., Li, C., Lai, Y., & Hung, M. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1892 · Cited by 289 · see citing works
“The core glycan is then trimmed and further processed in the ER and Golgi apparatus before the glycosylated protein is translocated to the cell membrane (10, 11).”
BackgroundMarinko, J. T., Huang, H., Penn, W. D., Capra, J. A., Schlebach, J. P., & Sanders, C. R. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00532 · Cited by 249 · see citing works
Isolated polycystic liver disease genes define effectors of polycystin-1 function
Besse, W., Dong, K., Choi, J., Punia, S., Fedeles, S. V., Choi, M., Gallagher, A.-R., Huang, E. B., Gulati, A., Knight, J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90129 · Cited by 203 · see citing works
Interfacing Materials Science and Biology for Drug Carrier Design
Such, G. K., Yan, Y., Johnston, A. P. R., Gunawan, S. T., & Caruso, F. (2015) · Advanced Materials · doi:10.1002/adma.201405084 · Cited by 219 · see citing works
Wada, R., Matsui, M., & Kawasaki, N. (2019) · mAbs · doi:10.1080/19420862.2018.1551044 · Cited by 186 · see citing works
“This heterogeneity is due to the different glycosyltransferase levels and gene expression profile in addition to the availability and spatial localization of nucleotide-sugar substrates in the cytoplasm.(3) N-glycosylation of mAbs is most frequently formed at a conserved asparagine residue located in the heavy chain c…”
BackgroundN-Linked Glycosylation in Archaea: a Structural, Functional, and Genetic Analysis
Jarrell, K. F., Ding, Y., Meyer, B. H., Albers, S., Kaminski, L., & Eichler, J. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00052-13 · Cited by 202 · see citing works
“11) with the structure -Glc-(1-4)- -6-sulfo-Qui-(1-3)- -GlcNAc[- -Man(1-6)][- -Man-(1-4)]-(1-4)- -GlcNAc (138), where sulfo-Qui is the rare sulfated sugar sulfoquinovose, previously found in photosynthetic membranes in chloroplasts and bacteria (155).”
InfluentialThe impact of PD-L1 N-linked glycosylation on cancer therapy and clinical diagnosis
Wang, Y., Lee, H., Hsu, J. L., Yu, D., & Hung, M. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00670-x · Cited by 196 · see citing works
Maruggi, G., Chiarot, E., Giovani, C., Buccato, S., Bonacci, S., Frigimelica, E., Margarit, I., Geall, A., Bensi, G., & Maione, D. (2017) · Vaccine · doi:10.1016/j.vaccine.2016.11.040 · Cited by 149 · see citing works
Cryo–electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B
Ramírez, A., Kowal, J., & Locher, K. (2019) · Science · doi:10.1126/science.aaz3505 · Cited by 147
Eukaryotic protein glycosylation: a primer for histochemists and cell biologists
Corfield, A. P. (2016) · Histochemistry and Cell Biology · doi:10.1007/s00418-016-1526-4 · Cited by 120 · see citing works
“In the ER lumen a series of manipulations occur to generate the range of N-glycans required for the tissue (Zuber and Roth 2009; Aebi 2013; Breitling and Aebi 2013).”
BackgroundInfluentialBerner, N., Reutter, K., & Wolf, D. H. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012749 · Cited by 125 · see citing works
Recent Findings in the Regulation of Programmed Death Ligand 1 Expression
Shen, X., Zhang, L., Li, J., Li, Y., Wang, Y., & Xu, Z. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01337 · Cited by 131 · see citing works
Guha, P., Kaptan, E., Gade, P., Kalvakolanu, D. V., & Ahmed, H. (2017) · Oncotarget · doi:10.18632/oncotarget.19277 · Cited by 121 · see citing works
“Within the endoplasmic reticulum (ER), nascent proteins are appropriately folded through the actions of a series of molecular chaperones, lectins, and glycosidases and travelled to the Golgi apparatus for further trafficking [1].”
BackgroundGlycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production
Zhao, X., Chen, H., & Wang, H. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.629873 · Cited by 101 · see citing works
“An asparagine residue can accept an oligosaccharide only if the residue is part of an AsnX-Ser or Asn-X-Thr sequence, in which X can be any residue except proline (Breitling and Aebi, 2013).”
BackgroundProtein Quality Control in the Endoplasmic Reticulum
Adams, B. M., Oster, M. E., & Hebert, D. N. (2019) · The Protein Journal · doi:10.1007/s10930-019-09831-w · Cited by 133 · see citing works
ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy
Xiao, X.-L., Shi, J., He, C., Bu, X., Sun, Y.-S., Gao, M., Xiang, B., Xiong, W., Dai, P., Mao, Q., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38605-3 · Cited by 88 · see citing works
“The N-linked glycosylation is a post-translational modi fi cation (PTM), which is crucial for membrane protein folding, stability, and localization 12,13 .”
Ninagawa, S., George, G., & Mori, K. (2020) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2020.129812 · Cited by 101 · see citing works
Protein Paucimannosylation Is an Enriched N‐Glycosylation Signature of Human Cancers
Chatterjee, S., Lee, L. Y., Kawahara, R., Abrahams, J. L., Adamczyk, B., Anugraham, M., Ashwood, C., Sumer-Bayraktar, Z., Briggs, M. T., Chik, J. H. L., et al. (2019) · Proteomics · doi:10.1002/pmic.201900010 · Cited by 73 · see citing works
Zhang, S. X., Ma, J. H., Bhatta, M., Fliesler, S. J., & Wang, J. J. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.12.001 · Cited by 79 · see citing works
“oligosaccharide to nascent polypeptide chains via oligosaccharyl transferase are separate biochemical events that occur in the ER, concomitant with or temporally associated with these folding and disulfide bond formation events (reviewed in (Breitling and Aebi 2013)).”
BackgroundHow glycosylation affects glycosylation: the role of N-glycans in glycosyltransferase activity.
Mikołajczyk, K., Kaczmarek, R., & Czerwinski, M. (2020) · Glycobiology · doi:10.1093/glycob/cwaa041 · Cited by 72 · see citing works
Protein Glycosylation Investigated by Mass Spectrometry: An Overview
Illiano, A., Pinto, G., Melchiorre, C., Carpentieri, A., Faraco, V., & Amoresano, A. (2020) · Cells · doi:10.3390/cells9091986 · Cited by 70
“To fully understand the origin of the diversity of glycan structures, it is necessary to deepen their biosynthetic transformations [5,6].”
BackgroundInfluentialEzeorba, T., Chukwudozie, K., Ezema, C. A., Anaduaka, E., Nweze, E., & Okeke, E. (2022) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2022.100075 · Cited by 69 · see citing works
Eleven residues determine the acyl chain specificity of ceramide synthases
Tidhar, R., Zelnik, I. D., Volpert, G., Ben-Dor, S., Kelly, S. L., Merrill, A., & Futerman, A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001936 · Cited by 65 · see citing works
“1C), where the first step in N-glycosylation takes place (20), as suggested in some but not all previous topological predictions (9, 17, 18).”
BackgroundKumar, A., Karuppagounder, S. S., Chen, Y., Corona, C., Kawaguchi, R., Cheng, Y., Balkaya, M., Sagdullaev, B. T., Wen, Z., Stuart, C., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.06.013 · Cited by 64 · see citing works
“53 These post-translational modifications occur as proteins (40%–60% of proteins, depending on the cell type) are translated into the ER.”
BackgroundTargeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro
Huang, H., Lai, Y., Liao, C., Wang, F.-Y., Huang, K.-B., Lee, I., Chou, W., Wang, S., Wang, L., Hsu, J.-M., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103712 · Cited by 61 · see citing works
“Glycosylation is an enzyme-directed site-specific process and Nglycosylation predominantly occurs at the consensus NXT/S motif [27].”
Towards understanding the extensive diversity of protein N ‐glycan structures in eukaryotes
Toustou, C., Walet-Balieu, M.-L., Kiefer-Meyer, M., Houdou, M., Lerouge, P., Foulquier, F., & Bardor, M. (2021) · Biological Reviews of The Cambridge Philosophical Society · doi:10.1111/brv.12820 · Cited by 61 · see citing works
Protein degradation corrects for imbalanced subunit stoichiometry in OST complex assembly
Mueller, S., Wåhlander, Å., Selevsek, N., Otto, C., Ngwa, E. M., Poljak, K., Frey, A. D., Aebi, M., & Gauss, R. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e15-03-0168 · Cited by 54 · see citing works
“Another complex, the oligosaccharyl transferase (OST), is the central enzyme of asparagine-linked (N-) glycosylation and attaches glycans to N-X-S/T sequons on proteins in the ER lumen (Breitling and Aebi, 2013).”
BackgroundSelf-citationWang, D.-Y., Wu, S.-Y., He, J.-X., Sun, L.-G., Zhu, H.-M., Zhang, Y., Liu, S., Duan, X., Wang, Y.-H., & Xu, T.-M. (2023) · Journal of experimental & clinical cancer research : CR · doi:10.1186/s13046-023-02758-2 · Cited by 59 · see citing works
“…(ER) and Golgi apparatus, where glycosyltransferases transfer N-acetylglucosamine to the N-X-T/S motif in the ER lumen, followed by PD-L1 transport to the Golgi apparatus for further maturation and folding by glycosidases, which translocate to the cell membrane to promote immune escape [25, 26].”
BackgroundLarge-scale characterization of intact N-glycopeptides using an automated glycoproteomic method.
Cheng, K., Chen, R., Seebun, D., Ye, M.-L., Figeys, D., & Zou, H.-F. (2014) · Journal of Proteomics · doi:10.1016/j.jprot.2014.08.006 · Cited by 59 · see citing works
“[39] Breitling J, Aebi M.”
BackgroundEsquivel, R. N., Schulze, S., Xu, R., Hippler, M., & Pohlschroder, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.693556 · Cited by 57 · see citing works
“N-Glycans are first assembled on a phosphorylated polyprenol lipid, followed by transfer of the assembled polysaccharide, by an oligosaccharyltransferase, to the target protein at an asparagine located in the consensus sequence NX(S/T) (4, 5).”
BackgroundGlycosylation of Immune Receptors in Cancer
Sun, R., Kim, A. M. J., & Lim, S. (2021) · Cells · doi:10.3390/cells10051100 · Cited by 58 · see citing works
“(4) Glycan maturation in Golgi [5,19].”
Strategies for Glycoengineering Therapeutic Proteins
Dammen-Brower, K., Epler, P., Zhu, S., Bernstein, Z. J., Stabach, P., Braddock, D., Spangler, J. B., & Yarema, K. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.863118 · Cited by 54 · see citing works
N-glycosylation of the protein disulfide isomerase Pdi1 ensures full Ustilago maydis virulence
Marín-Menguiano, M., Moreno-Sánchez, I., Barrales, R. R., Fernández-Álvarez, A., & Ibeas, J. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007687 · Cited by 54 · see citing works
“N-glycosylation consists of the addition of an oligosaccharide core, composed of two N-acetylglucosamines (NAcGlc), nine mannoses (Man) and three glucose (Glc) molecules, NAcGlc2Man9Glc3, to the nitrogen chain of an asparagine residue in the sequence Asn-x-Ser/Thr, where x can be any amino acid except proline [9,10].”
BackgroundN-glycosylation, a leading role in viral infection and immunity development
Pandey, V. K., Sharma, R., Prajapati, G., Mohanta, T., & Mishra, A. K. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07359-4 · Cited by 53 · see citing works
“Glycosyltransferases (GTase) further adds three glucose residues to this growing oligosaccharide chain [16], forming an oligosaccharide precursor, Glc3Man9GlcNAc2 (Supplementary 1) which get transferred to Asn residues in the tripeptide sequences Asn-X-Ser/Thr (where X = Any amino acid excluding proline) of proteins […”
BackgroundPolycystic liver disease: Classification, diagnosis, treatment process, and clinical management
Zhang, Z.-Y., Wang, Z.-M., & Huang, Y. (2020) · World Journal of Hepatology · doi:10.4254/wjh.v12.i3.72 · Cited by 53
Zelnik, I. D., Rozman, B., Rosenfeld-Gur, E., Ben-Dor, S., & Futerman, A. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-21162-2_4 · Cited by 48 · see citing works
Human protein paucimannosylation: cues from the eukaryotic kingdoms
Tjondro, H. C., Loke, I., Chatterjee, S., & Thaysen-Andersen, M. (2019) · Biological Reviews of The Cambridge Philosophical Society · doi:10.1111/brv.12548 · Cited by 46 · see citing works
“…the structure, localisation, biosynthesis and functions of the canonical types of N -glycoproteins, their biological involvement in human health and disease, and their phylogenetic differences across species (Kreisman & Cobb, 2012; Breitling & Aebi, 2013; Chung et al., 2017; Varki, 2017).”
BackgroundN-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment
Duan, Z., Shi, R.-H., Gao, B., & Cai, J. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05502-2 · Cited by 45 · see citing works
“N-linked glycosylation refers to the attachment of glycans to the nitrogen (N) atom of an asparagine (Asn) residue in a protein, which plays a critical role in protein localization and secretion, immunogenicity and the immune response [35, 36].”
BackgroundWang, S., Xu, Y., Li, Z., Zhang, S., Lim, J., Lee, K. O., Li, C., Qian, Q., Jiang, D. A., & Qi, Y. (2014) · The Plant Journal · doi:10.1111/tpj.12497 · Cited by 56 · see citing works
“A well-conserved pathway for processing oligosaccharides in the ER has been identified in eukaryotic model organisms (Lehle et al., 2006; Song et al., 2011; Breitling and Aebi, 2013).”
BackgroundData Independent Analysis of IgG Glycoforms in Samples of Unfractionated Human Plasma
Sanda, M., & Goldman, R. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b02554 · Cited by 44
Genetic defects in dolichol metabolism
Buczkowska, A., Świeżewska, E., & Lefeber, D. J. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9760-1 · Cited by 42 · see citing works
“…enzymes participating in the synthesis and modification of the LLO and respective genes have been described in numerous excellent reviews (e.g. Haeuplte and Hennet 2009; Banerjee 2012; Aebi 2013; Breitling and Aebi 2013), only a brief summary on selected steps of the LLO pathway is presented below.”
BackgroundInfluentialChen, Q., Denard, B., Lee, C.-E., Han, S., Ye, J. S., & Ye, J. (2016) · Molecules and Cells · doi:10.1016/j.molcel.2016.06.032 · Cited by 41 · see citing works
“Since N-linked glycosylation only occurs in the lumen of the ER (Breitling and Aebi, 2013), the results shown above suggest that loop 3 of TM4SF20(B) is located in the ER lumen, whereas the same loop in TM4SF20(A) is exposed to the cytosol.”
BackgroundProtein glycosylation during infection by plant pathogenic fungi.
Liu, C.-Y., Talbot, N. J., & Chen, X.-L. (2021) · New Phytologist · doi:10.1111/nph.17207 · Cited by 40 · see citing works
The role of antibody glycosylation in autoimmune and alloimmune kidney diseases
Beyze, A., Larroque, C., & Quintrec, M. L. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00850-0 · Cited by 42 · see citing works
Engineering of Yeast Glycoprotein Expression
Wachter, C. D., Landuyt, L. V., & Callewaert, N. (2018) · Advances in biochemical engineering, biotechnology · doi:10.1007/10_2018_69 · Cited by 43 · see citing works
Unusual glycosylation of proteins: Beyond the universal sequon and other amino acids.
Dutta, D., Mandal, C., & Mandal, C. (2017) · Biochimica et Biophysica Acta - General Subjects · doi:10.1016/j.bbagen.2017.08.025 · Cited by 39 · see citing works
LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review
Sánchez-León, M., Loaeza-Reyes, K. J., Matias-Cervantes, C. A., Mayoral-Andrade, G., Pérez-Campos, E., Pérez-Campos-Mayoral, L., Hernández-Huerta, M. T., Zenteno, E., Pérez-Cervera, Y., & Pina-Canseco, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105276 · Cited by 38 · see citing works
“The N -glycosylation process includes two principal phases: assembling a lipid-linked oligosaccharide (LLO) and transferring the oligosaccharide to selected asparagine residues of polypeptide chains [10].”
BackgroundRegulation of PD-L1 Trafficking from Synthesis to Degradation
Lemma, E. Y., Letian, A., Altorki, N. K., & McGraw, T. E. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0953 · Cited by 37 · see citing works
Ramírez, A., Boilevin, J., Lin, C.-W., Gan, B.-H., Janser, D., Aebi, M., Darbre, T., Reymond, J., & Locher, K. (2017) · Glycobiology · doi:10.1093/glycob/cwx045 · Cited by 37
“During protein N-glycosylation, glycans from lipid-linked oligosaccharides (LLOs) are transferred onto asparagine residues located in N-glycosylation sequons (Breitling and Aebi 2013).”
BackgroundSelf-citationInfluence of protein/glycan interaction on site‐specific glycan heterogeneity
Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T., Gauss, R., Morbidelli, M., & Aebi, M. (2017) · The FASEB Journal · doi:10.1096/fj.201700403r · Cited by 36 · see citing works
Self-citationPanoutsopoulou, K., Thiagarajah, S., Zengini, E., Day-Williams, A., Ramos, Y. F. M., Meessen, J., Huétink, K., Nelissen, R., Southam, L., Rayner, N. W., et al. (2016) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2016-210373 · Cited by 36 · see citing works
Emerging structural insights into C-type glycosyltransferases.
Alexander, J. A., & Locher, K. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102547 · Cited by 35 · see citing works
Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity
Ojha, R., & Prajapati, V. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30483 · Cited by 35 · see citing works
“X‐Ser/Thr (X‐ amino acid except for proline) (Breitling & Aebi, 2013).”
New and potential strategies for the treatment of PMM2-CDG
Gámez, A., Serrano, M., Gallego, D., Vilas, A., & Pérez, B. (2020) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2020.129686 · Cited by 41 · see citing works
Perneel, J., & Rademakers, R. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02486-5 · Cited by 35 · see citing works
“It was shown that N–X–T is glycosylated more efficiently than N–X–S [7], which raises the possibility that the p.”
BackgroundYu, R., Longo, J., van Leeuwen, J. E., Zhang, C.-J., Branchard, E., Elbaz, M., Cescon, D., Drake, R., Dennis, J., & Penn, L. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-2642 · Cited by 34 · see citing works
Ramírez, A., Boilevin, J., Biswas, R., Gan, B.-H., Janser, D., Aebi, M., Darbre, T., Reymond, J., & Locher, K. (2017) · Glycobiology · doi:10.1093/glycob/cwx017 · Cited by 34
“Protein N-glycosylation confers a multitude of functions to the acceptor macromolecules, facilitating diverse interactions and signaling pathways (Kelleher and Gilmore 2006; Breitling and Aebi 2013; Xu and Ng 2015; Cherepanova et al. 2016).”
BackgroundSelf-citationHuang, L.-F., Tan, C.-C., Yeh, J., Liu, H.-Y., Liu, Y.-K., Ho, S., & Lu, C.-A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140812 · Cited by 34
The chemistry and biology of mycolactones
Gehringer, M., & Altmann, K. (2017) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.13.159 · Cited by 33
Glycans in autophagy, endocytosis and lysosomal functions
Reggiori, F., Gabius, H., Aureli, M., Römer, W., Sonnino, S., & Eskelinen, E. (2021) · Glycoconjugate Journal · doi:10.1007/s10719-021-10007-x · Cited by 37 · see citing works
“Once on the protein, this N-glycan is trimmed down stepwise to a heptasaccharide (Man5GlcNAc2) in the ER, and finally re-elongated into the diversity of mature N-glycans by a series of glycosylation steps taking place in the Golgi cisternae [55].”
BackgroundXiang, T., Yang, G.-L., Liu, X., Zhou, Y., Fu, Z.-X., Lu, F., Gu, J.-G., Taniguchi, N., Tan, Z., Chen, X., et al. (2017) · Biochimica et Biophysica Acta - General Subjects · doi:10.1016/j.bbagen.2017.02.014 · Cited by 32 · see citing works
Fischbach, H., Döring, M., Nikles, D., Lehnert, E., Baldauf, C., Kalinke, U., & Tampé, R. (2015) · Nature Communications · doi:10.1038/ncomms7199 · Cited by 32
Regulation of PD-L1 glycosylation and advances in cancer immunotherapy
Lee, T.-A., Tsai, E.-Y., Liu, S.-H., Chou, W., Hung, S.-D. H., Chang, C.-Y., Chao, C.-H., Yamaguchi, H., Lai, Y., Chen, H.-L., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.217498 · Cited by 27 · see citing works
A Potential Lock-Type Mechanism for Unconventional Secretion in Fungi
Reindl, M., Hänsch, S., Weidtkamp-Peters, S., & Schipper, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030460 · Cited by 31
“On their route, proteins are often subject to pathway-specific post-translational modifications like N-glycosylation or disulfide bond formation [2,3].”
BackgroundGlycan Microarrays of Fluorescently-Tagged Natural Glycans
Song, X.-Z., Heimburg-Molinaro, J., Smith, D. F., & Cummings, R. (2015) · Glycoconjugate Journal · doi:10.1007/s10719-015-9584-8 · Cited by 31 · see citing works
“of high mannose-, hybrid- and complex-type N-glycans in mammals [29, 30].”
Role of Myeloperoxidase, Oxidative Stress, and Inflammation in Bronchopulmonary Dysplasia
Wu, T.-J., Jing, X., Teng, M., Pritchard, K. A., Day, B. W., Naylor, S., & Teng, R. (2024) · Antioxidants · doi:10.3390/antiox13080889 · Cited by 31 · see citing works
“These findings reasonably explain the impaired angiogenesis in the rat BPD model since both VEGF-VEGFR2 signaling [101] and endothelial cell oxidative phosphorylation [102] are critical for successful angiogenesis.”
BackgroundPosttranslational Modifications in PD-L1 Turnover and Function: From Cradle to Grave
Yu, X., Li, W., Young, K. H., & Li, Y. (2021) · Biomedicines · doi:10.3390/biomedicines9111702 · Cited by 31 · see citing works
“In this process, initial trimming of the precursor molecule occurs in the ER by oligosaccharyltransferase, which transfers a 14-sugar core glycan from dolichol to an asparagine residue of an N-X-T/S motif (asparagine-any amino acid except proline-threonine/serine) in newly synthesized nascent proteins that have entere…”
BackgroundTrends in oligomannosylation and α1,2-mannosidase expression in human cancers
Chatterjee, S., Ugonotti, J., Lee, L. Y., Everest-Dass, A., Kawahara, R., & Thaysen-Andersen, M. (2021) · OncoTarget · doi:10.18632/oncotarget.28064 · Cited by 30 · see citing works
Ramírez, A., & Locher, K. (2023) · Glycobiology · doi:10.1093/glycob/cwad053 · Cited by 29 · see citing works
“N -glycans play essential roles in protein folding, trafficking, and cell–cell communication (Nothaft and Szymanski 2010; Breitling and Aebi 2013; Cherepanova et al. 2016; Varki 2017).”
BackgroundControl of STIM and Orai function by post-translational modifications
Johnson, J., Blackman, R., Gross, S., & Soboloff, J. (2022) · Cell Calcium · doi:10.1016/j.ceca.2022.102544 · Cited by 30 · see citing works
Singh, R., Almutairi, M. M., Pacheco-Andrade, R., Almiahuob, M. Y. M., & Difulvio, M. (2015) · International Journal of Cell Biology · doi:10.1155/2015/505294 · Cited by 29
Regulation of Cancer Immune Checkpoints: Molecular and Cellular Mechanisms and Therapy
Xu, J. (2020) · doi:10.1007/978-981-15-3266-5 · Cited by 29
Site-specific N-glycosylation of integrin α2 mediates collagen-dependent cell survival
Huang, Y.-L., Liang, C.-Y., Labitzky, V., Ritz, D., Oliveira, T., Cumin, C., Estermann, M., Lange, T., Everest-Dass, A., & Jacob, F. (2021) · iScience · doi:10.1016/j.isci.2021.103168 · Cited by 27
Thak, E. J., Lee, S.-B., Xu-Vanpala, S., Lee, D.-J., Chung, S. Y., Bahn, Y., Oh, D., Shinohara, M. L., & Kang, H. A. (2020) · mBio · doi:10.1128/mbio.00711-20 · Cited by 27 · see citing works
“Thus, Alg9 has a dual function in lipid-linked N-glycan biosynthesis (31).”
TUSC3: a novel tumour suppressor gene and its functional implications
Yu, X.-S., Zhai, C.-J., Fan, Y.-J., Zhang, J.-D., Liang, N., Liu, F.-J., Cao, L., Wang, J., & Du, J. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13128 · Cited by 27 · see citing works
“The most significant cancer-associated function of TUSC3 is associated with the vital role of OST catalysing in the protein N-glycosylation process, which is tightly linked to the proper folding of nascent peptides shuttling and quality control [4, 16, 18].”
BackgroundChang, M. M., Imperiali, B., Eichler, J., & Guan, Z.-Q. (2015) · PLoS ONE · doi:10.1371/journal.pone.0130482 · Cited by 27 · see citing works
“Across evolution, N-linked glycans are initially assembled on cytoplasmically-oriented phosphorylated polyisoprenoids before delivery to target proteins in the lumen of the endoplasmic reticulum in eukaryotes, in the periplasm in bacteria and on the external surface of the cell in archaea [8,20,21].”
BackgroundGlucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control
Longo, J., DeCamp, L. M., Oswald, B. M., Teis, R., Reyes-Oliveras, A., Dahabieh, M. S., Ellis, A. E., Vincent, M. P., Damico, H. N., Gallik, K. L., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.07.006 · Cited by 28 · see citing works
Interplay Between Metabolic Pathways and Increased Oxidative Stress in Human Red Blood Cells
Spinelli, S., Marino, A., Morabito, R., & Remigante, A. (2024) · Cells · doi:10.3390/cells13232026 · Cited by 27 · see citing works
Recent advances in expression and purification strategies for plant made vaccines
Venkataraman, S., Khan, I. H., Habibi, P., Le, M., Lippert, R., & Hefferon, K. L. (2023) · Frontiers in Plant Science · doi:10.3389/fpls.2023.1273958 · Cited by 31 · see citing works
“Secretory proteins undergo additional modi fi cations in the endoplasmic reticulum (ER) and Golgi apparatus, including N-glycosylation (Faye et al., 2005; Breitling and Aebi, 2013).”
BackgroundThe role of protein glycosylation in the occurrence and outcome of acute ischemic stroke
Li, J., Qiu, Y., Zhang, C., Wang, H., Bi, R., Wei, Y., Li, Y., & Hu, B. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106726 · Cited by 28 · see citing works
Jiao, Q., Chen, T.-S., Niu, G., Zhang, H., Zhou, C.-F., & Hong, Z. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa321 · Cited by 26
Jasmonic acid‐inducible TSA1 facilitates ER body formation
Geem, K. R., Kim, D. H., Lee, D. W., Kwon, Y., Lee, J.-H., Kim, J. H., & Hwang, I. (2018) · The Plant Journal · doi:10.1111/tpj.14112 · Cited by 26
Ceramide synthases: Reflections on the impact of Dr. Lina M. Obeid
Kim, J. L., Mestre, B., Shin, S.-H., & Futerman, A. H. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.109958 · Cited by 25 · see citing works
Genetics of polycystic liver diseases
Lee, P. Y., van de Laarschot, L. F. M., Bañales, J. M., & Drenth, J. P. H. (2019) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000514 · Cited by 33 · see citing works
Genetic dissection of the secretory route followed by a fungal extracellular glycosyl hydrolase
Hernández-González, M., Pantazopoulou, A., Spanoudakis, D., Seegers, C., & Peñalva, M. (2018) · Molecular Microbiology · doi:10.1111/mmi.14073 · Cited by 25
PD-1/PD-L1 Checkpoints and Resveratrol: A Controversial New Way for a Therapeutic Strategy
Delmas, D., Hermetet, F., & Aires, V. (2021) · Cancers · doi:10.3390/cancers13184509 · Cited by 24
“reaction that begins in the endoplasmic reticulum (ER), in which the oligosaccharyltransferase (OST) complex transfers a 14-sugar moiety, Glc3Man9GlcNAc2 (Glc, glucose; Man, mannose; GlcNAc, N-acetylglucosamine), from dolichol lipid to the Asn residue in the consensus Asn-X-Ser/Thr motif within the nascent polypeptide…”
BackgroundLi, M., Liu, X.-Y., Liu, Z., Sun, Y., Liu, M.-X., Wang, X., Zhang, H.-F., Zheng, X.-B., & Zhang, Z.-G. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162243 · Cited by 24
“N-linked glycosylation is a process of ubiquitous protein modification in eukaryotic cells, and results in a systemic modification of the proteome [6].”
BackgroundYang, M., d'Ortoli, T. A., Säwén, E., Jana, M., Widmalm, G., & MacKerell, A. D. (2016) · Physical Chemistry, Chemical Physics - PCCP · doi:10.1039/c6cp02970a · Cited by 24
Uncovering Flavivirus Host Dependency Factors through a Genome-Wide Gain-of-Function Screen
Petrova, E., Gracias, S., Beauclair, G., Tangy, F., & Jouvenet, N. (2019) · Viruses · doi:10.3390/v11010068 · Cited by 23
“DDOST is a part of the oligosaccharyltransferase (OST) machinery that catalyzes the N-linked glycolysation of newly-synthetized proteins in the ER [29].”
BackgroundN-linked glycosylation of flavivirus E protein contributes to viral particle formation
Ishida, K., Yagi, H., Kato, Y., & Morita, E. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011681 · Cited by 24 · see citing works
“N-glycosylation is a post-translational modification that occurs in secreted and membrane-bound proteins and involves a consensus protein motif (N-X-S/T, where X is not proline) [38].”
BackgroundLucas, P., Dumontier, R., Loutelier‐Bourhis, C., Mareck, A., Afonso, C., Lerouge, P., Mati‐Baouche, N., & Bardor, M. (2018) · Plant Methods · doi:10.1186/s13007-018-0374-8 · Cited by 28 · see citing works
“They respectively correspond to sodium and potassium adducts of a Hex11HexNAc2 structure, differing by one hexose residue from the Glc3Man9GlcNAc2 LLO precursor identified in mammals and land plants [9, 11, 44].”
Background
- Authors
- Breitling, J., & Aebi, M.
- Affiliations
- ETH Zurich (CH)
- ORCID
- Aebi, M.
- Venue
- Cold Spring Harbor Perspectives in Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-06-10
- Volume
- 5
- Issue
- 8
- Pages
- a013359-a013359
- ISSN
- 1943-0264 (ISSN-L)
- PMC
- PMC3721281
- OpenAlex
- W2133197373
- Cited by
- 332
- References
- 0
- Citations by year
- 2026: 33 · 2025: 36 · 2024: 40 · 2023: 33 · 2022: 29 · 2021: 35 · 2020: 27 · 2019: 25 · 2018: 16 · 2017: 20 · 2016: 12 · 2015: 16 · 2014: 9
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cold Spring Harbor Perspectives in Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- N-glycosylation, endoplasmic reticulum, lipid-linked oligosaccharides, oligosaccharyltransferase, asparagine-linked glycosylation, glycosyltransferases, N-glycoproteome, Saccharomyces cerevisiae, protein glycosylation
- MeSH terms
- Asparagine, Endoplasmic Reticulum, Glycosylation, Hexosyltransferases, Membrane Proteins, Oligosaccharides, Saccharomyces cerevisiae, Signal Transduction, Glycosyltransferases
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