Imperial College London

DrWengangChai

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2596w.chai

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

163 results found

Chai W, 2022, Development of high-throughput UPLC-MS/MS using multiple reaction monitoring for quantitation of complex human milk oligosaccharides and application to large population survey of secretor status and Lewis blood group, Food Chemistry, Vol: 397, Pages: 1-9, ISSN: 0308-8146

Human milk oligosaccharides (HMOs) have attracted increasing attention due to the emerging evidence of their positive roles for infant’s health. A high-throughput method for absolute quantitation of the complex HMOs including multiple isomeric structures is important but very challenging, due to the highly divers nature and wide variation in content of HMOs from different individuals. Here we used UPLC-MS-MRM in the negative-ion mode for accurate quantitation of 23 complex HMOs in just 15 min. The selected oligosaccharides are in their native forms and include neutral and sialylated, fucosylated and non-fucosylated, linear and branched, and secretor and Lewis phenotype indicators. The well validated method with good sensitivity, recovery and reproducibility was then applied to a large population quantitative survey of 251 Chinese mothers from five different ethnic groups (Han, Zhuang, Hui, Mongolian and Tibetan) living in different geographical regions for their secretor’s status and Lewis phenotypes.

Journal article

Han K, Yue Y, Wang W, Wang F, Chai W, Zhao S, Yu Met al., 2022, Lewis x-Carrying O-glycans are Candidate Modulators for Conceptus Attachment in Pigs., Biol Reprod

Successful attachment of conceptus to the uterine luminal epithelium (LE) is crucial for establishing a functional placenta in pigs. However, the underlying mechanisms are yet to be elucidated. The uterine LE-conceptus interface is enriched in various glycoconjugates essential to implantation. Using MALDI-MS profiling, we identified for the first time the O-glycan repertoire in pig endometrium during the conceptus attachment stage. The expression pattern of blood group A, O(H), Lewis x, y, a, b (Lex, Ley, Lea, and Leb), the sialylated and sulfated Lex antigens in the uterine LE-conceptus interface was assessed using immunofluorescence assays. Notably, the Lex-carrying O-glycans exhibited a temporal-spatial expression pattern. They were absent in the endometrium on estrous cycle days but strongly and spatially presented in the conceptus and uterine LE to which the conceptus apposes during the early conceptus attachment stage. In addition, Lex-carrying O-glycans were co-localized with secreted phosphoprotein 1 (SPP1), a well-characterized factor that plays a role in promoting conceptus attachment through interacting with integrin αVβ3 and integrin αVβ6. Meanwhile, the immunoprecipitation assays revealed an interaction between the Lex-carrying O-glycans and SPP1, integrin αV, and integrin β6. Furthermore, we provided evidence that the β1,4-galactosyltransferase 1 (B4GALT1) gene is a potential regulator for Lex antigen expression in the uterine LE-conceptus interface during the early conceptus attachment stage. In conclusion, our findings show that Lex-carrying O-glycans, presumably dependent on B4GALT1 gene expression, might modulate conceptus attachment by interacting with the SPP1-integrin receptor complex in pigs.

Journal article

Zheng Y, Zhao J, Li J, Guo Z, Sheng J, Ye X, Jin G, Wang C, Chai W, Yan J, Liu D, Liang Xet al., 2021, SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate, INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Vol: 193, Pages: 1124-1129, ISSN: 0141-8130

Journal article

McAllister N, Liu Y, Silva LM, Lentscher AJ, Chai W, Wu N, Griswold KA, Raghunathan K, Vang L, Alexander J, Warfield KL, Diamond MS, Feizi T, Silva LA, Dermody TSet al., 2021, Chikungunya Virus Strains from Each Genetic Clade Bind Sulfated Glycosaminoglycans as Attachment Factors (vol 94, e01500-20, 2020), JOURNAL OF VIROLOGY, Vol: 95, ISSN: 0022-538X

Journal article

Correia VG, Trovao F, Pinheiro BA, Bras JLA, Silva LM, Nunes C, Coimbra MA, Liu Y, Feizi T, Fontes CMGA, Mulloy B, Chai W, Carvalho AL, Palma ASet al., 2021, Mapping Molecular Recognition of beta 1,3-1,4-Glucans by a Surface Glycan-Binding Protein from the Human Gut Symbiont Bacteroides ovatus, MICROBIOLOGY SPECTRUM, Vol: 9, ISSN: 2165-0497

Journal article

Huang C, Tan Z, Zhao K, Zou W, Wang H, Gao H, Sun S, Bu D, Chai W, Li Yet al., 2021, The effect of N-glycosylation of SARS-CoV-2 spike protein on the virus interaction with the host cell ACE2 receptor, iScience, Vol: 24, Pages: 1-15, ISSN: 2589-0042

The densely glycosylated spike (S) protein highly exposed on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) surface mediates host cell entry by binding to the receptor angiotensin-converting enzyme 2 (ACE2). However, the role of glycosylation has not been fully understood. In this study, we investigated the effect of different N-glycosylation of S1 protein on its binding to ACE2. Using real-time surface plasmon resonance assay the negative effects were demonstrated by the considerable increase of binding affinities of de-N-glycosylated S1 proteins produced from three different expression systems including baculovirus-insect, Chinese hamster ovarian and two variants of human embryonic kidney 293 cells. Molecular dynamic simulations of the S1 protein-ACE2 receptor complex revealed the steric hindrance and Coulombic repulsion effects of different types of N-glycans on the S1 protein interaction with ACE2. The results should contribute to future pathological studies of SARS-CoV-2 and therapeutic development of Covid-19, particularly using recombinant S1 proteins as models.

Journal article

Gyapon-Quast F, Goicoechea de Jorge E, Malik T, Wu N, Yu J, Chai W, Feizi T, Liu Y, Pickering MCet al., 2021, Defining the glycosaminoglycan interactions of complement factor H-related protein 5, Journal of Immunology, Vol: 207, Pages: 534-541, ISSN: 0022-1767

Complement activation is an important mediator of kidney injury in glomerulonephritis. Complement factor H (FH) and FH-related protein 5 (FHR-5) influence complement activation in C3 glomerulopathy and IgA nephropathy by differentially regulating glomerular complement. FH is a negative regulator of complement C3 activation. Conversely, FHR-5 in vitro promotes C3 activation either directly or by competing with FH for binding to complement C3b. The FH-C3b interaction is enhanced by surface glycosaminoglycans (GAGs) and the FH-GAG interaction is well-characterized. In contrast, the contributions of carbohydrates to the interaction of FHR-5 and C3b are unknown. Using plate-based and microarray technologies we demonstrate that FHR-5 interacts with sulfated GAGs and that this interaction is influenced by the pattern and degree of GAG sulfation. The FHR-5-GAG interaction that we identified has functional relevance as we could show that the ability of FHR-5 to prevent binding of FH to surface C3b is enhanced by surface kidney heparan sulfate. Our findings are important in understanding the molecular basis of the binding of FHR-5 to glomerular complement and the role of FHR-5 in complement-mediated glomerular disease.

Journal article

Chai W, Li C, Palma A, Zhang P, Zhang Y, Gao C, Silva L, Li Z, Trovao F, Weishaupt M, Seeberger P, Likhosherstov L, Piskarev V, Yu J, Westerlind Uet al., 2021, Noncovalent microarrays from synthetic amino-terminating glycans: Implications in expanding glycan microarray diversity and platform comparison, Glycobiology, Vol: 31, Pages: 931-946, ISSN: 0959-6658

Glycan microarrays have played important roles in detection and specificity assignment of glycan recognition by proteins. However, the size and diversity of glycan libraries in current microarray systems are small compared to estimated glycomes, and these may lead to missed detection or incomplete assignment. For microarray construction, covalent and noncovalent immobilization are the two types of methods used, but a direct comparison of results from the two platforms is required. Here we develop a chemical strategy to prepare lipid-linked probes from both naturally derived aldehyde-terminating and synthetic amino-terminating glycans that addresses the two aspects: expansion of sequence-defined glycan libraries and comparison of the two platforms. We demonstrate the specific recognition by plant and mammalian lectins, carbohydrate-binding modules and antibodies and the overall similarities from the two platforms. Our results provide new knowledge on unique glycan-binding specificities for the immune receptor Dectin-1 toward β-glucans and the interaction of rotavirus P[19] adhesive protein with mucin O-glycan cores.

Journal article

Li J, Jiang M, Zhou J, Ding J, Guo Z, Li M, Ding F, Chai W, Yan J, Liang Xet al., 2021, Characterization of rat and mouse acidic milk oligosaccharides based on hydrophilic interaction chromatography coupled with electrospray tandem mass spectrometry, Carbohydrate Polymers, Vol: 259, ISSN: 0144-8617

Oligosaccharides are one of the most important components in mammalian milk. Milk oligosaccharides can promote colonization of gut microbiota and protect newborns from infections. The diversity and structures of MOs differ among mammalian species. MOs in human and farm animals have been well-documented. However, the knowledge on MOs in rat and mouse have been very limited even though they are the most-widely used models for studies of human physiology and disease. Herein, we use a high-sensitivity online solid-phase extraction and HILIC coupled with electrospray tandem mass spectrometry to analyze the acidic MOs in rat and mouse. Among the fifteen MOs identified, twelve were reported for the first time in rat and mouse together with two novel sulphated oligosaccharides. The complete list of acidic oligosaccharides present in rat and mouse milk is the baseline information of these animals and should contribute to biological/biomedical studies using rats and mice as models.

Journal article

Murugesan G, Correia VG, Palma AS, Chai W, Li C, Ten F, Martin E, Laux B, Franz A, Fuchs K, Weigle B, Crocker PRet al., 2021, Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression, GLYCOBIOLOGY, Vol: 31, Pages: 44-54, ISSN: 0959-6658

Journal article

McAllister N, Liu Y, Silva LM, Lentscher AJ, Chai W, Wu N, Griswold KA, Raghunathan K, Vang L, Alexander J, Warfield KL, Diamond MS, Feizi T, Silva LA, Dermody TSet al., 2020, Chikungunya virus strains from each genetic clade bind sulfated glycosaminoglycans as attachment factors, Journal of Virology, Vol: 94, ISSN: 0022-538X

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell-surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors. However, the specific types of GAGs and potentially other glycans to which CHIKV binds and whether there are strain-specific differences in GAG binding is not fully understood. To identify the types of glycans bound by CHIKV, we conducted glycan microarray analyses and discovered that CHIKV preferentially binds GAGs. Microarray results also indicate that sulfate groups on GAGs are essential for CHIKV binding and that CHIKV binds most strongly to longer GAG chains of heparin and heparan sulfate. To determine whether GAG-binding capacity varies among CHIKV strains, a representative strain from each genetic clade was tested. While all strains directly bound to heparin and chondroitin sulfate in ELISAs and depended on heparan sulfate for efficient cell-binding and infection, we observed some variation by strain. Enzymatic removal of cell-surface GAGs and genetic ablation that diminishes GAG expression reduced CHIKV binding and infectivity of all strains. Collectively, these data demonstrate that GAGs are the preferred glycan bound by CHIKV, enhance our understanding of the specific GAG moieties required for CHIKV binding, define strain differences in GAG engagement, and provide further evidence for a critical function of GAGs in CHIKV cell attachment and infection.IMPORTANCE Alphavirus infections are a global health threat, contributing to outbreaks of disease in many parts of the world. Recent epidemics caused by CHIKV, an arthritogenic alphavirus, resulted in more than 8.5 million cases as the virus has spread into new geographic regions, including the Western Hemisphere. CHIKV causes disease in the majority of people infected, leading

Journal article

Ribeiro DO, Viegas A, Pires VMR, MedeirosSilva J, Bule P, Chai W, Marcelo F, Fontes CMGA, Cabrita EJ, Palma AS, Carvalho ALet al., 2020, Molecular basis for the preferential recognition of β1,3‐1,4‐glucans by the family 11 carbohydrate‐binding module from <i>Clostridium thermocellum</i>, The FEBS Journal, Vol: 287, Pages: 2723-2743, ISSN: 1742-464X

Journal article

Huang C, Wang H, Bu D, Zhou J, Dong J, Zhang J, Gao H, Wang Y, Chai W, Sun S, Li Yet al., 2020, Multistage mass spectrometry with intelligent precursor selection for N-glycan branching pattern analysis, CARBOHYDRATE POLYMERS, Vol: 237, ISSN: 0144-8617

Journal article

Huang C, Sun S, Yan J, Wang H, Zhou J, Gao H, Xie W, Li Y, Chai Wet al., 2020, Identification of carbohydrate peripheral epitopes important for recognition by positive-ion MALDI multistage mass spectrometry, CARBOHYDRATE POLYMERS, Vol: 229, ISSN: 0144-8617

Journal article

Vendele I, Willment JA, Silva LM, Palma AS, Chai W, Liu Y, Feizi T, Spyrou M, Stappers MHT, Brown GD, Gow NARet al., 2020, Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls, PLoS Pathogens, Vol: 16, Pages: 1-29, ISSN: 1553-7366

During the course of fungal infection, pathogen recognition by the innate immune system is critical to initiate efficient protective immune responses. The primary event that triggers immune responses is the binding of Pattern Recognition Receptors (PRRs), which are expressed at the surface of host immune cells, to Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in the fungal cell wall. Most fungi have mannosylated PAMPs in their cell walls and these are recognized by a range of C-type lectin receptors (CTLs). However, the precise spatial distribution of the ligands that induce immune responses within the cell walls of fungi are not well defined. We used recombinant IgG Fc-CTLs fusions of three murine mannan detecting CTLs, including dectin-2, the mannose receptor (MR) carbohydrate recognition domains (CRDs) 4–7 (CRD4-7), and human DC-SIGN (hDC-SIGN) and of the β-1,3 glucan-binding lectin dectin-1 to map PRR ligands in the fungal cell wall of fungi grown in vitro in rich and minimal media. We show that epitopes of mannan-specific CTL receptors can be clustered or diffuse, superficial or buried in the inner cell wall. We demonstrate that PRR ligands do not correlate well with phylogenetic relationships between fungi, and that Fc-lectin binding discriminated between mannosides expressed on different cell morphologies of the same fungus. We also demonstrate CTL epitope differentiation during different phases of the growth cycle of Candida albicans and that MR and DC-SIGN labelled outer chain N-mannans whilst dectin-2 labelled core N-mannans displayed deeper in the cell wall. These immune receptor maps of fungal walls of in vitro grown cells therefore reveal remarkable spatial, temporal and chemical diversity, indicating that the triggering of immune recognition events originates from multiple physical origins at the fungal cell surface.

Journal article

Gao T, Yan J, Liu C-C, Palma AS, Guo Z, Xiao M, Chen X, Liang X, Chai W, Cao Het al., 2019, Chemoenzymatic Synthesis of O-Mannose Glycans Containing Sulfated or Nonsulfated HNK-1 Epitope, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 141, Pages: 19351-19359, ISSN: 0002-7863

Journal article

Sun X, Dang L, Li D, Qi J, Wang M, Chai W, Zhang Q, Wang H, Bai R, Tan M, Duan Zet al., 2019, Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus, VIROLOGICA SINICA, Vol: 35, Pages: 156-170, ISSN: 1674-0769

Journal article

Wu N, Silva LM, Liu Y, Zhang Y, Gao C, Zhang F, Fu L, Peng Y, Linhardt R, Kawasaki T, Mulloy B, Chai W, Feizi T, Wu N, Silva LM, Liu Y, Zhang Y, Gao C, Zhang F, Fu L, Peng Y, Linhardt R, Kawasaki T, Mulloy B, Chai W, Feizi Tet al., 2019, Glycan Markers of Human Stem Cells Assigned with Beam Search Arrays., Mol Cell Proteomics, Vol: 18, Pages: 1981-2002, ISSN: 1535-9476

Glycan antigens recognized by monoclonal antibodies have served as stem cell markers. To understand regulation of their biosynthesis and their roles in stem cell behavior precise assignments are required. We have applied state-of-the-art glycan array technologies to compare the glycans bound by five antibodies that recognize carbohydrates on human stem cells. These are: FC10.2, TRA-1-60, TRA-1-81, anti-i and R-10G. Microarray analyses with a panel of sequence-defined glycans corroborate that FC10.2, TRA-1-60, TRA-1-81 recognize the type 1-(Galβ-3GlcNAc)-terminating backbone sequence, Galβ-3GlcNAcβ-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc, and anti-i, the type 2-(Galβ-4GlcNAc) analog, Galβ-4GlcNAcβ-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc, and we determine substituents they can accommodate. They differ from R-10G, which requires sulfate. By Beam Search approach, starting with an antigen-positive keratan sulfate polysaccharide, followed by targeted iterative microarray analyses of glycan populations released with keratanases and mass spectrometric monitoring, R-10G is assigned as a mono-sulfated type 2 chain with 6-sulfation at the penultimate N-acetylglucosamine, Galβ-4GlcNAc(6S)β-3Galβ-4GlcNAcβ-3Galβ-4GlcNAc. Microarray analyses using newly synthesized glycans corroborate the assignment of this unique determinant raising questions regarding involvement as a ligand in the stem cell niche.

Journal article

Huang C, Yan J, Zhan L, Zhao M, Zhou J, Gao H, Xie W, Li Y, Chai Wet al., 2019, Linkage and sequence analysis of neutral oligosaccharides by negative-ion MALDI tandem mass spectrometry with laser-induced dissociation, ANALYTICA CHIMICA ACTA, Vol: 1071, Pages: 25-35, ISSN: 0003-2670

Journal article

Cong X, Sun X-M, Qi J-X, Li H-B, Chai W-G, Zhang Q, Wang H, Kong X-Y, Song J, Pang L-L, Jin M, Li D-D, Tan M, Duan Z-Jet al., 2019, GII.13/21 Noroviruses Recognize Glycans with a Terminal beta-Galactose via an Unconventional Glycan Binding Site, JOURNAL OF VIROLOGY, Vol: 93, ISSN: 0022-538X

Journal article

Yan J, Ding J, Jin G, Duan Z, Yang F, Li D, Zhou H, Li M, Guo Z, Chai W, Liang Xet al., 2019, Profiling of Human Milk Oligosaccharides for Lewis Epitopes and Secretor Status by Electrostatic Repulsion Hydrophilic Interaction Chromatography Coupled with Negative-Ion Electrospray Tandem Mass Spectrometry, ANALYTICAL CHEMISTRY, Vol: 91, Pages: 8199-8206, ISSN: 0003-2700

Journal article

Li Z, Chai W, 2019, Mucin O-glycan microarrays, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 56, Pages: 187-197, ISSN: 0959-440X

Journal article

Chandra N, Liu Y, Liu J-X, Fraengsmyr L, Wu N, Silva LM, Lindstrom M, Chai W, Domellof FP, Feizi T, Arnberg Net al., 2019, Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37, Viruses, Vol: 11, ISSN: 1999-4915

Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.

Journal article

Li S, Li J, Mao G, Wu T, Lin D, Hu Y, Ye X, Tian D, Chai W, Linhardt RJ, Chen Set al., 2019, Fucosylated chondroitin sulfate from Isostichopus badionotus alleviates metabolic syndromes and gut microbiota dysbiosis induced by high-fat and high-fructose diet, INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Vol: 124, Pages: 377-388, ISSN: 0141-8130

Journal article

Sun S, Huang C, Wang Y, Liu Y, Zhang J, Zhou J, Gao F, Yang F, Chen R, Mulloy B, Chai W, Li Y, Bu Det al., 2018, Toward Automated Identification of Glycan Branching Patterns Using Multistage Mass Spectrometry with Intelligent Precursor Selection, ANALYTICAL CHEMISTRY, Vol: 90, Pages: 14412-14422, ISSN: 0003-2700

Journal article

Loureiro LR, Sousa DP, Ferreira D, Chai W, Lima L, Pereira C, Lopes CB, Correia VG, Silva LM, Li C, Santos LL, Ferreira JA, Barbas A, Palma AS, Novo C, Videira PAet al., 2018, Novel monoclonal antibody L2A5 specifically targeting sialyl-Tn and short glycans terminated by alpha-2–6 sialic acids, Scientific Reports, Vol: 8, ISSN: 2045-2322

Incomplete O-glycosylation is a feature associated with malignancy resulting in the expression of truncated glycans such as the sialyl-Tn (STn) antigen. Despite all the progress in the development of potential anti-cancer antibodies, their application is frequently hindered by low specificities and cross-reactivity. In this study, a novel anti-STn monoclonal antibody named L2A5 was developed by hybridoma technology. Flow cytometry analysis showed that L2A5 specifically binds to sialylated structures on the cell surface of STn-expressing breast and bladder cancer cell lines. Moreover, immunoblotting assays demonstrated reactivity to tumour-associated O-glycosylated proteins, such as MUC1. Tumour recognition was further observed using immunohistochemistry assays, which demonstrated a high sensitivity and specificity of L2A5 mAb towards cancer tissue, using bladder and colorectal cancer tissues. L2A5 staining was exclusively tumoural, with a remarkable reactivity in invasive and metastasis sites, not detectable by other anti-STn mAbs. Additionally, it stained 20% of cases of triple-negative breast cancers, suggesting application in diseases with unmet clinical needs. Finally, the fine specificity was assessed using glycan microarrays, demonstrating a highly specific binding of L2A5 to core STn antigens and additional ability to bind 2–6-linked sialyl core-1 probes. In conclusion, this study describes a novel anti-STn antibody with a unique binding specificity that can be applied for cancer diagnostic and future development of new antibody-based therapeutic applications.

Journal article

Sun X, Li D, Qi J, Chai W, Wang L, Wang L, Peng R, Wang H, Zhang Q, Pang L, Kong X, Wang H, Jin M, Gao GF, Duan Zet al., 2018, Glycan Binding Specificity and Mechanism of Human and Porcine P[6]/P[19] Rotavirus VP8*s, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

Journal article

Sun X, Wang L, Qi J, Li D, Wang M, Cong X, Peng R, Chai W, Zhang Q, Wang H, Wen H, Gao GF, Tan M, Duan Zet al., 2018, Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands, JOURNAL OF VIROLOGY, Vol: 92, ISSN: 0022-538X

Journal article

Chai W, Zhang Y, Mauri L, Ciampa MG, Mulloy B, Sonnino S, Feizi Tet al., 2018, Assignment by Negative-Ion Electrospray Tandem Mass Spectrometry of the Tetrasaccharide Backbones of Monosialylated Glycans Released from Bovine Brain Gangliosides, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 29, Pages: 1308-1318, ISSN: 1044-0305

Gangliosides, as plasma membrane-associated sialylated glycolipids, are antigenic structures and they serve as ligands for adhesion proteins of pathogens, for toxins of bacteria, and for endogenous proteins of the host. The detectability by carbohydrate-binding proteins of glycan antigens and ligands on glycolipids can be influenced by the differing lipid moieties. To investigate glycan sequences of gangliosides as recognition structures, we have underway a program of work to develop a “gangliome” microarray consisting of isolated natural gangliosides and neoglycolipids (NGLs) derived from glycans released from them, and each linked to the same lipid molecule for arraying and comparative microarray binding analyses. Here, in the first phase of our studies, we describe a strategy for high-sensitivity assignment of the tetrasaccharide backbones and application to identification of eight of monosialylated glycans released from bovine brain gangliosides. This approach is based on negative-ion electrospray mass spectrometry with collision-induced dissociation (ESI-CID-MS/MS) of the desialylated glycans. Using this strategy, we have the data on backbone regions of four minor components among the monosialo-ganglioside-derived glycans; these are of the ganglio-, lacto-, and neolacto-series.

Journal article

Lenman A, Liaci AM, Liu Y, Frangsmyr L, Frank M, Blaum BS, Chai W, Podgorski II, Harrach B, Benko M, Feizi T, Stehle T, Arnberg Net al., 2018, Polysialic acid is a cellular receptor for human adenovirus 52, Proceedings of the National Academy of Sciences of the United States of America, Vol: 115, Pages: E4264-E4273, ISSN: 0027-8424

Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.

Journal article

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