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| Item Type: | Article |
|---|---|
| Title: | Pathogen-sugar interactions revealed by universal saturation transfer analysis |
| Creators Name: | Buchanan, C.J., Gaunt, B., Harrison, P.J., Yang, Y., Liu, J., Khan, A., Giltrap, A.M., Le Bas, A., Ward, P.N., Gupta, K., Dumoux, M., Tan, T.K., Schimaski, L., Daga, S., Picchiotti, N., Baldassarri, M., Benetti, E., Fallerini, C., Fava, F., Giliberti, A., Koukos, P.I., Davy, M.J., Lakshminarayanan, A., Xue, X., Papadakis, G., Deimel, L.P., Casablancas-Antràs, V., Claridge, T.D.W., Bonvin, A.M.J.J., Sattentau, Q.J., Furini, S., Gori, M., Huo, J., Owens, R.J., Schaffitzel, C., Berger, I., Renieri, A., Naismith, J.H., Baldwin, A.J. and Davis, B.G. |
| Abstract: | Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis. |
| Keywords: | Biomolecular Nuclear Magnetic Resonance, COVID-19, Coronavirus Spike Glycoprotein, Cryoelectron Microscopy, Genetic Variation, Host-Pathogen Interactions, Polysaccharides, Protein Binding, Protein Domains, SARS-CoV-2, Sialic Acids |
| Source: | Science |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 377 |
| Number: | 6604 |
| Page Range: | eabm3125 |
| Date: | 22 July 2022 |
| Official Publication: | https://doi.org/10.1126/science.abm3125 |
| PubMed: | View item in PubMed |
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