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Histo-Blood Group Antigen Presentation Is Critical for Binding of Norovirus VLP to Glycosphingolipids in Model Membranes
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- Nasir, Waqas (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,University of Gothenburg
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- Frank, M. (författare)
- Biognos AB
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- Kunze, Angelika, 1978 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Bally, Marta, 1981 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Parra, F. (författare)
- Universidad de Oviedo,University of Oviedo
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- Nyholm, Per-Georg, 1958 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,Biognos AB,University of Gothenburg
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- Höök, Fredrik, 1966 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Larson, Göran, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,University of Gothenburg
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(creator_code:org_t)
- 2017-03-27
- 2017
- Engelska.
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Ingår i: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 12:5, s. 1288-1296
- Relaterad länk:
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http://dx.doi.org/10...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://research.cha...
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Abstract
Ämnesord
Stäng
- Virus entry depends on biomolecular recognition at the surface of cell membranes. In the case of glycolipid receptors, these events are expected to be influenced by how the glycan epitope close to the membrane is presented to the virus. This presentation of membrane associated glycans is more restricted than that of glycans in solution, particularly because of orientational constraints imposed on the glycolipid through its lateral interactions with other membrane lipids and proteins. We have developed and employed a total internal reflection fluorescence microscopy-based binding assay and. a scheme for molecular dynamics (MD) membrane simulations to investigate the consequences of various glycan presentation effects. The system studied was histo-blood group antigen (HBGA) epitopes of membrane-bound glycosphingolipids (GSLs) derived from small intestinal epithelium of humans (type 1 chain) and dogs (type 2 chain) interacting with GII.4 norovirus-like particles. Our experimental results showed strong binding to all lipid-linked type 1 chain HBGAs but no or only weak binding to the corresponding type 2 chain HBGAs. This is in contrast to results derived from STD experiments with free HBGAs in solution where binding was observed for Lewis x. The MD data suggest that the strong binding to type 1 chain glycolipids was due to the well-exposed (1,2)-linked alpha-L-Fucp and (1,4)- linked alpha-L-Fucp residues, while the weaker binding or lack of binding to type 2 chain HBGAs was due to the very restricted accessibility of the (1,3) -linked alpha-L-Fucp residue when the glycolipid is embedded in a phospholipid membrane. Our results not only contribute to a general understanding of protein carbohydrate interactions on model membrane surfaces, particularly in the context of virus binding, but also suggest a possible role of human intestinal GSLs as potential receptors for norovirus uptake.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
Nyckelord
- molecular-dynamics simulations
- epithelial-cells
- glycolipid receptors
- small-intestine
- secretor fut2
- abo-phenotype
- group-a
- virus
- surface
- lewis
- Biochemistry & Molecular Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Nasir, Waqas
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Frank, M.
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Kunze, Angelika, ...
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Bally, Marta, 19 ...
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Parra, F.
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Nyholm, Per-Geor ...
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Höök, Fredrik, 1 ...
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Larson, Göran, 1 ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Fysik
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och Annan fysik
- Artiklar i publikationen
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Acs Chemical Bio ...
- Av lärosätet
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Göteborgs universitet
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Chalmers tekniska högskola