| 1. |
- Nordgren, Johan, et al.
(författare)
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Both lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner.
- 2014
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 59:11, s. 1567-73
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Tidskriftsartikel (refereegranskat)abstract
- The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo-blood group antigens (HBGAs) in an RV genotype-dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy.
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| 2. |
- Nilsson, Jonas, 1970, et al.
(författare)
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Synthetic standard aided quantification and structural characterization of amyloid-beta glycopeptides enriched from cerebrospinal fluid of Alzheimer's disease patients
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- An early pathological hallmark of Alzheimer's disease (AD) is amyloid-beta (A beta) deposits in the brain, which largely consist of up to 43 amino acids long A beta peptides derived from the amyloid precursor protein (APP). We previously identified a series of sialylated Tyr-10 O-glycosylated A beta peptides, 15-20 residues long, from human cerebrospinal fluid (CSF) and observed a relative increase of those in AD vs non-AD patients. We report here on the synthesis and use of an isotopically double-labeled A beta 1-15 glycopeptide, carrying the core 1Gal beta 3GalNAc alpha 1-O-Tyr-10 structure, to (1) identify by HCD LC-MS/MS the definite glycan core 1 structure of immunopurified and desialylated A beta glycopeptides in human CSF and to (2) establish a LC-MS/MS quantification method for desialylated A beta 1-15 (and A beta-17) glycopeptides and to (3) compare the concentrations of these A beta glycopeptides in CSF from 20 AD patients and 20 healthy controls. Although we unambiguously identified the core 1 structures and Tyr-10 attachment sites of the glycopeptides, we did not observe any quantitative differences, determined through both peptide and oxonium ion fragments, of the desialylated A beta 1-15 or A beta 1-17 glycopeptides between the AD and non-AD group. The new quantitative glycoproteomic approach described, using double-labeled glycopeptide standards, will undoubtedly facilitate future studies of glycopeptides as clinical biomarkers but should also embrace sialylated A beta standards to reveal specific sialylation patterns of individual A beta glycopeptides in AD patients and controls.
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| 3. |
- Nilsson, Jonas, 1970, et al.
(författare)
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Targeting the glycoproteome.
- 2013
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Ingår i: Glycoconjugate journal. - : Springer Science and Business Media LLC. - 1573-4986 .- 0282-0080. ; 30:2, s. 119-36
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Tidskriftsartikel (refereegranskat)abstract
- Despite numerous original publications describing the structural complexity of N- and O-linked glycans on glycoproteins, only very few answer the basic question of which particular glycans are linked to which amino acid residues along the polypeptide chain. Such structural information is of fundamental importance for understanding the biological roles of complex glycosylations as well as deciphering their non-template driven biosynthesis. This review focuses on presenting and commenting on recent strategies, specifically aimed at identifying the glycoproteome of cultured cells and biological samples, using targeted and global enrichment procedures and utilizing the high resolution power, high through-put capacity and complementary fragmentation techniques of tandem mass spectrometry. The goal is to give an update of this emerging field of protein and glyco-sciences and suggest routes to bridge the data gap between the two aspects of glycoprotein characteristics, i.e. glycan structures and their attachment sites.
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| 4. |
- Halim, Adnan, et al.
(författare)
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LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins.
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:2, s. 573-584
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Tidskriftsartikel (refereegranskat)abstract
- The GalNAc O-glycosylation on Ser/Thr residues of extracellular proteins has not been well characterized from a proteomics perspective. We previously reported a sialic acid capture-and-release protocol to enrich tryptic N- and O-glycopeptides from human cerebrospinal fluid glycoproteins using nanoLC-ESI-MS/MS with collision-induced dissociation (CID) for glycopeptide characterization. Here, we have introduced peptide N-glycosidase F (PNGase F) pre-treatment of CSF samples to remove the N-glycans facilitating the selective characterization of O-glycopeptides and enabling the use of an automated CID-MS2/MS3 search protocol for glycopeptide identification. We used electron capture and transfer dissociation (ECD/ETD) to pinpoint the glycosylation site(s) of the glycopeptides, identified as predominantly core 1 like HexHexNAc-O- glycans attached to 1-4 Ser/Thr residues. We characterized 108 O-glycosylations and found Pro residues preferentially in the n-1, n+1 and/or n+3 positions in relation to the Ser/Thr attachment site (n). The characterization of glycans and glycosylation sites in glycoproteins from human clinical samples provides a basis for future studies addressing the biological and diagnostic importance of specific protein glycosylations in relation to human disease.
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| 5. |
- Parveen, Nagma, 1988, et al.
(författare)
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Competition for Membrane Receptors: Norovirus Detachment via Lectin Attachment
- 2019
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:41, s. 16303-16311
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Tidskriftsartikel (refereegranskat)abstract
- Virus internalization into the host cells occurs via multivalent interactions, in which a single virus binds to multiple receptors in parallel. Because of analytical and experimental limitations this complex type of interaction is still poorly understood and quantified. Herein, the multivalent interaction of norovirus-like particles (noroVLPs) with H or B type 1 glycosphingolipids (GSLs), embedded in a supported phospholipid bilayer, is investigated by following the competition between noroVLPs and a lectin (from Ralstonia solanacearum) upon binding to these GSLs. Changes in noroVLP and lectin coverage, caused by competition, were monitored for both GSLs and at different GSL concentrations using quartz crystal microbalance with dissipation monitoring. The study yields information about the minimum GSL concentration needed for (i) noroVLPs to achieve firm attachment to the bilayer prior to competition and to (ii) remain firmly attached to the bilayer during competition. We show that these two concentrations are almost identical for the H type 1-noroVLP interaction but differ for B type 1, indicating an accumulation of B type 1 GSLs in the noroVLP-bilayer interaction area. Furthermore, the GSL concentration required for firm attachment is significantly larger for H type 1 than for B type 1, indicating a higher affinity of noroVLP toward B type 1. This finding is supported by extracting the energy of single noroVLP-H type 1 and noroVLP-B type 1 bonds from the competition kinetics, which were estimated to be 5 and 6 kcal/mol, respectively. This demonstrates the potential of utilizing competitive binding kinetics to analyze multivalent interactions, which has remained difficult to quantify using conventional approaches.
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| 6. |
- Persson, Andrea, et al.
(författare)
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Glycosaminoglycan Domain Mapping of Cellular Chondroitin/Dermatan Sulfates
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Glycosaminoglycans (GAGs) are polysaccharides produced by most mammalian cells and involved in a variety of biological processes. However, due to the size and complexity of GAGs, detailed knowledge about the structure and expression of GAGs by cells, the glycosaminoglycome, is lacking. Here we report a straightforward and versatile approach for structural domain mapping of complex mixtures of GAGs, GAGDoMa. The approach is based on orthogonal enzymatic depolymerization of the GAGs to generate internal, terminating, and initiating domains, and nanoflow reversed-phase ion-pairing chromatography with negative mode higher-energy collision dissociation (HCD) tandem mass spectrometry (MS/MS) for structural characterization of the individual domains. GAGDoMa provides a detailed structural insight into the glycosaminoglycome, and offers an important tool for deciphering the complexity of GAGs in cellular physiology and pathology. © 2020, The Author(s).
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| 7. |
- Bally, Marta, 1981, et al.
(författare)
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Interaction of virions with membrane glycolipids
- 2012
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3967 .- 1478-3975. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Cellular membranes contain various lipids including glycolipids (GLs). The hydrophilic head groups of GLs extend from the membrane into the aqueous environment outside the cell where they act as recognition sites for specific interactions. The first steps of interaction of virions with cells often include contacts with GLs. To clarify the details of such contacts, we have used the total internal reflection fluorescence microscopy to explore the interaction of individual unlabelled virus-like particles (or, more specifically, norovirus protein capsids), which are firmly bound to a lipid bilayer, and fluorescent vesicles containing glycosphingolipids (these lipids form a subclass of GLs). The corresponding binding kinetics were earlier found to be kinetically limited, while the detachment kinetics were logarithmic over a wide range of time. Here, the detachment rate is observed to dramatically decrease with increasing concentration of glycosphingolipids from 1% to 8%. This effect has been analytically explained by using a generic model describing the statistics of bonds in the contact area between a virion and a lipid membrane. Among other factors, the model takes the formation of GL domains into account. Our analysis indicates that in the system under consideration, such domains, if present, have a characteristic size smaller than the contact area between the vesicle and the virus-like particle.
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| 8. |
- Bucardo, Filemon, et al.
(författare)
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Susceptibility of Children to Sapovirus Infections, Nicaragua, 2005–2006
- 2012
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Ingår i: Emerging Infectious Diseases. - Atlanta, GA, USA : U.S. Department of Health and Human Services * Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:11, s. 1875-1878
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Tidskriftsartikel (refereegranskat)abstract
- We describe the genetic diversity of sapovirus (SaV) in children in Nicaragua and investigate the role of host genetic factors and susceptibility to SaV infections. Our results indicate that neither ABO blood group, Lewis phenotype, nor secretor status affects susceptibility to SaV infection in Nicaragua.
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| 9. |
- Nordén, Rickard, 1977, et al.
(författare)
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O-linked glycosylation of the mucin domain of the herpes simplex virus type 1 specific glycoprotein gC-1 is temporally regulated in a seed-and-spread manner.
- 2015
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 290:8, s. 5078-5091
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Tidskriftsartikel (refereegranskat)abstract
- The herpes simplex virus type 1 (HSV-1) glycoprotein gC-1, participating in viral receptor interactions and immunity interference, harbors a mucin-like domain with multiple clustered O-linked glycans. Using HSV-1 infected diploid human fibroblasts, an authentic target for HSV-1 infection, and a protein immunoaffinity procedure, we enriched fully glycosylated gC-1 and a series of its biosynthetic intermediates. This fraction was subjected to trypsin digestion and a LC-MS/MS glycoproteomics approach. In parallel, we characterized the expression patterns of the 20 isoforms of human GalNAc transferases responsible for initiation of O-linked glycosylation. The gC-1 O-glycosylation was regulated in an orderly manner initiated by synchronous addition of one GalNAc unit each to T87 and T91, and one GalNAc unit to either T99 or T101, forming a core glycopeptide for subsequent additions of in all 11 GalNAc residues to selected Ser and Thr residues of the T76-L107 stretch of the mucin domain. The expression patterns of GalNAc transferases in the infected cells suggested that initial additions of GalNAc were carried out by initiating GalNAc transferases, in particular GalNAc-T2, whereas subsequent GalNAc additions were carried out by follow up transferases, in particular GalNAc-T10. Essentially all of the susceptible Ser or Thr residues had to acquire their GalNAc units before any elongation to longer O-linked glycans of the gC-1-associated GalNAc units was permitted. Since the GalNAc occupancy pattern is of relevance for receptor binding of gC-1, the data provides a model to delineate biosynthetic steps of O-linked glycosylation of the gC-1 mucin domain in HSV-1 infected target cells.
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| 10. |
- Syx, Delfien, et al.
(författare)
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Alterations in glycosaminoglycan biosynthesis associated with the Ehlers-Danlos syndromes.
- 2022
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 323:6, s. C1843-C1859
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Tidskriftsartikel (refereegranskat)abstract
- Proteoglycans consist of a core protein substituted with one or more glycosaminoglycan (GAG) chains and execute versatile functions during many physiological and pathological processes. The biosynthesis of GAG chains is a complex process that depends on the concerted action of a variety of enzymes. Central to the biosynthesis of heparan sulfate (HS) and chondroitin sulfate/dermatan sulfate (CS/DS) GAG chains is the formation of a tetrasaccharide linker region followed by biosynthesis of HS or CS/DS-specific repeating disaccharide units, which then undergo modifications and epimerization. The importance of these biosynthetic enzymes is illustrated by several severe pleiotropic disorders that arise upon their deficiency. The Ehlers-Danlos syndromes (EDS) constitute a special group among these disorders. Although most EDS types are caused by defects in fibrillar types I, III, or V collagen, or their modifying enzymes, a few rare EDS types have recently been linked to defects in GAG biosynthesis. Spondylodysplastic EDS (spEDS) is caused by defective formation of the tetrasaccharide linker region, either due to β4GalT7 or β3GalT6 deficiency, whereas musculocontractural EDS (mcEDS) results from deficiency of D4ST1 or DS-epi1, impairing DS formation. This narrative review highlights the consequences of GAG deficiency in these specific EDS types, summarizes the associated phenotypic features and the molecular spectrum of reported pathogenic variants, and defines the current knowledge on the underlying pathophysiological mechanisms based on studies in patient-derived material, in vitro analyses, and animal models.
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