Pathogen-sugar interactions revealed by universal saturation transfer analysis.

Autor: Buchanan CJ; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.; Kavli Institute of Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK., Gaunt B; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK., Harrison PJ; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK.; Diamond Light Source, Harwell Science and Innovation Campus, Oxfordshire, UK., Yang Y; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Liu J; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK., Khan A; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK., Giltrap AM; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK., Le Bas A; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Ward PN; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Gupta K; Max Planck Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK., Dumoux M; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK., Tan TK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., Schimaski L; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., Daga S; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Picchiotti N; Department of Information Engineering and Mathematics, University of Siena, Siena, Italy.; Department of Mathematics, University of Pavia, Pavia, Italy., Baldassarri M; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Benetti E; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Fallerini C; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Fava F; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy., Giliberti A; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Koukos PI; Bijvoet Centre for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands., Davy MJ; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK., Lakshminarayanan A; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK., Xue X; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.; Sir William Dunn School of Pathology, Oxford, UK., Papadakis G; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK., Deimel LP; Sir William Dunn School of Pathology, Oxford, UK., Casablancas-Antràs V; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.; Kavli Institute of Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK., Claridge TDW; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK., Bonvin AMJJ; Bijvoet Centre for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands., Sattentau QJ; Sir William Dunn School of Pathology, Oxford, UK., Furini S; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy., Gori M; Department of Information Engineering and Mathematics, University of Siena, Siena, Italy.; Maasai, I3S CNRS, Université Côte d'Azur, Nice, France., Huo J; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Owens RJ; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Schaffitzel C; Bijvoet Centre for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands., Berger I; Bijvoet Centre for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands., Renieri A; Medical Genetics, University of Siena, Siena, Italy.; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy., Naismith JH; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK., Baldwin AJ; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.; Kavli Institute of Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK., Davis BG; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.; Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2022 Jul 22; Vol. 377 (6604), pp. eabm3125. Date of Electronic Publication: 2022 Jul 22.
DOI: 10.1126/science.abm3125
Abstrakt: 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.
Databáze: MEDLINE
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