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  • Pathogen-sugar interactions...
    Buchanan, Charles J; Gaunt, Ben; Harrison, Peter J; Yang, Yun; Liu, Jiwei; Khan, Aziz; Giltrap, Andrew M; Le Bas, Audrey; Ward, Philip N; Gupta, Kapil; Dumoux, Maud; Tan, Tiong Kit; Schimaski, Lisa; Daga, Sergio; Picchiotti, Nicola; Baldassarri, Margherita; Benetti, Elisa; Fallerini, Chiara; Fava, Francesca; Giliberti, Annarita; Koukos, Panagiotis I; Davy, Matthew J; Lakshminarayanan, Abirami; Xue, Xiaochao; Papadakis, Georgios; Deimel, Lachlan P; Casablancas-Antràs, Virgínia; Claridge, Timothy D W; Bonvin, Alexandre M J J; Sattentau, Quentin J; Furini, Simone; Gori, Marco; Huo, Jiandong; Owens, Raymond J; Schaffitzel, Christiane; Berger, Imre; Renieri, Alessandra; Naismith, James H; Baldwin, Andrew J; Davis, Benjamin G

    Science, 07/2022, Letnik: 377, Številka: 6604
    Journal Article

    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.