Pathogen-sugar interactions revealed by universal saturation transfer analysis

Pathogen-sugar interactions revealed by universal saturation transfer analysis

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 compound with known experimental constraints. 'Universal saturation transfer analysis' (uSTA)...

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Bibliographic Details
Main Authors: Buchanan, CJ, Gaunt, B, Harrison, PJ, Yang, Y, Liu, J, Khan, A, Giltrap, AM, Le Bas, A, Ward, PN, Gupta, K, Dumoux, M, Tan, TK, Schimaski, L, Daga, S, Picchiotti, N, Baldassarri, M, Benetti, E, Fallerini, C, Fava, F, Giliberti, A, Koukos, PI, Davy, MJ, Lakshminarayanan, A, Xue, X, Papadakis, G, Deimel, LP, Casablancas-Antràs, V, Claridge, TDW, Bonvin, AMJJ, Sattentau, QJ, Furini, S, Gori, M, Huo, J, Owens, RJ, Schaffitzel, C, Berger, I, Renieri, A, Naismith, JH, Baldwin, AJ, Davis, BG
Other Authors: GEN-COVID Multicenter Study
Format: Journal article
Language:English
Published: American Association for the Advancement of Science 2022
Description
Summary: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 compound 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 SARS-CoV-2 spike trimer binds sialoside sugars in an 'end-on' manner. uSTA-guided modelling 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 in deeper human lung as potentially relevant to virulence and/or zoonosis.

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