Mechanistic reconstruction of glycoprotein secretion through monitoring of intracellular N-glycan processing

Arigoni-Affolter, Ilaria; Scibona, Ernesto; Lin, Chi Feng; Brühlmann, David; Souquet, Jonathan; Broly, Hervé; Aebi, Markus

doi:10.1126/sciadv.aax8930

Cited by 41 publications

(46 citation statements)

References 57 publications

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“…While all glycans that are added to proteins through attachment to asparagine side chains (N-linked glycans) are transferred en bloc as a single glycan precursor structure, subsequent passage of the nascent glycoprotein through the cellular machinery (Endoplasmic reticulum, Golgi apparatus) exposes the glycans to enzymes, glycosidases and glycosyl transferases, that modify their structure. The ability of enzymes to alter or process each glycan depends in part on the 3D shape of the protein to which the glycan is attached, particularly in the region of the glycosite 16,20,21 , and on the time that any given glycan is exposed to these enzymes 20,22 . The presence of multiple glycosites and the variation in the composition of the glycans at a glycosite, can result in a staggering number of permutations of protein glycoforms.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Grant

Montgomery

Ito

et al. 2020

Preprint

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Here we have generated 3D structures of glycoforms of the spike (S) protein SARS-CoV-2, based on reported 3D structures for the S protein and on reported glycomics data for the protein produced in HEK293 cells. We also report structures for glycoforms that represent those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi and ER), as well as those that are commonly observed on antigens present in other viruses.These models were subjected to MD simulation to take into account protein and glycan plasticity, and to determine the extent to which glycan microheterogeneity impacts antigenicity. Lastly, we have identified peptides in the S protein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine.

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Section: Resultsmentioning

confidence: 99%

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Grant

Montgomery

Ito

et al. 2020

Preprint

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“…N-linked protein glycosylation is a topic of interest in plant science [1][2][3][4][5][6][7] as it can modify various biological functions [8,9], and affect growth, physiology, and development of living organisms. N-glycans are linked to asparagine residues in eukaryotic proteins [4].…”

Section: Introductionmentioning

confidence: 99%

Determination of complex type free, non‐conjugated oligosaccharide glucose unit values in tomato xylem sap for early detection of nutrient deficiency

Mátyás¹,

Singer²,

Szarka

et al. 2020

Electrophoresis

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Although knowledge on glycan biosynthesis and processing is continuously maturing, there are still a limited number of studies that examine biological functions of N‐glycan structures in plants, which remain virtually unknown. Here, the statistical correlation between nutrient (nitrogen) deficiency symptoms of crops and changes in 8‐aminopyrene‐1,3,6‐trisulfonic acid (APTS)‐labeled complex type free oligosaccharides is reported. While deficiency symptoms are predicted by multispectral images and Kjeldahl digestion, APTS‐labeled complex type free oligosaccharides are identified by their glucose unit (GU) values in tomato xylem sap, using capillary electrophoresis with laser induced fluorescence detection (CE‐LIF). Given the limited number of structures obtained from plants, archived in the literature, in the future, it is intended to create an open access database of promising indicators, namely, glycan structures that are presumably responsible for the nutrient deficiency caused stress in plants (http://glycoplants.org).

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“…The eukaryotic secretory pathway is organized such that glycoproteins are exposed for a limited time to processing enzymes located in different compartments of the pathway [37][38][39]. Therefore, site-specific initial processing velocities are a determining factor for N-glycan processing in vivo, together with the residence times of glycoproteins in the individual compartments of the secretory pathway.…”

Section: Discussionmentioning

confidence: 99%

Glycan-Protein Interactions Determine Kinetics ofN-Glycan Remodeling

Mathew

Weiss

Giese

et al. 2020

Preprint

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A hallmark of N-linked glycosylation in the secretory compartments of eukaryotic cells is the sequential remodeling of an initially uniform oligosaccharide to a site-specific, heterogeneous ensemble of glycostructures on mature proteins. To understand site-specific processing, we used protein disulfide isomerase (PDI), a model protein with five glycosylation sites, for molecular dynamics (MD) simulations and compared the result to a biochemical in vitro analysis with four different glycan processing enzymes. As predicted by an analysis of the accessibility of the N-glycans for their processing enzymes derived from the MD simulations, N-glycans at different glycosylation sites showed different kinetic properties for the processing enzymes. In addition, altering the tertiary structure context of N-glycan substrates affected N-glycan remodeling in a site-specific way. We propose that differential, tertiary structure context dependent N-glycan reactivities lead to different glycan structures in the same protein through kinetically controlled processing pathways.

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Mechanistic reconstruction of glycoprotein secretion through monitoring of intracellular N-glycan processing

Cited by 41 publications

References 57 publications

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Determination of complex type free, non‐conjugated oligosaccharide glucose unit values in tomato xylem sap for early detection of nutrient deficiency

Glycan-Protein Interactions Determine Kinetics ofN-Glycan Remodeling

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