Pathogen-sugar interactions revealed by universal saturation transfer analysis

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.; Davis, B.G.

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Tools

Preview	PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 3MB
	Other (Supplementary Materials) 30MB

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

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year