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| Item Type: | Article |
|---|---|
| Title: | Pathogen-sugar interactions revealed by universal saturation transfer analysis |
| Creators Name: | Buchanan, C.J. and Gaunt, B. and Harrison, P.J. and Yang, Y. and Liu, J. and Khan, A. and Giltrap, A.M. and Le Bas, A. and Ward, P.N. and Gupta, K. and Dumoux, M. and Tan, T.K. and Schimaski, L. and Daga, S. and Picchiotti, N. and Baldassarri, M. and Benetti, E. and Fallerini, C. and Fava, F. and Giliberti, A. and Koukos, P.I. and Davy, M.J. and Lakshminarayanan, A. and Xue, X. and Papadakis, G. and Deimel, L.P. and Casablancas-Antràs, V. and Claridge, T.D.W. and Bonvin, A.M.J.J. and Sattentau, Q.J. and Furini, S. and Gori, M. and Huo, J. and Owens, R.J. and Schaffitzel, C. and Berger, I. and Renieri, A. and Naismith, J.H. and 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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