Your browser doesn't support javascript.
Pathogen-sugar interactions revealed by universal saturation transfer analysis.
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.
  • Buchanan CJ; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Gaunt B; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
  • Harrison PJ; Kavli Institute of Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK.
  • Yang Y; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Liu J; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK.
  • Khan A; Diamond Light Source, Harwell Science and Innovation Campus, Oxfordshire, UK.
  • Giltrap AM; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Le Bas A; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK.
  • Ward PN; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Gupta K; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Dumoux M; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
  • Tan TK; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Schimaski L; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
  • Daga S; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Picchiotti N; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK.
  • Baldassarri M; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Headington, Oxford OX3 7BN, UK.
  • Benetti E; Max Planck Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK.
  • Fallerini C; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Fava F; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Giliberti A; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
  • Koukos PI; Medical Genetics, University of Siena, Siena, Italy.
  • Davy MJ; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Lakshminarayanan A; Department of Information Engineering and Mathematics, University of Siena, Siena, Italy.
  • Xue X; Department of Mathematics, University of Pavia, Pavia, Italy.
  • Papadakis G; Medical Genetics, University of Siena, Siena, Italy.
  • Deimel LP; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Casablancas-Antràs V; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Claridge TDW; Medical Genetics, University of Siena, Siena, Italy.
  • Bonvin AMJJ; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Sattentau QJ; Medical Genetics, University of Siena, Siena, Italy.
  • Furini S; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Gori M; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
  • Huo J; Medical Genetics, University of Siena, Siena, Italy.
  • Owens RJ; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • Schaffitzel C; Bijvoet Centre for Biomolecular Research, Faculty of Science, Utrecht University, Utrecht, Netherlands.
  • Berger I; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Renieri A; Rosalind Franklin Institute, Harwell Science and Innovation Campus, Oxford OX11 0FA, UK.
  • Naismith JH; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
  • Baldwin AJ; Sir William Dunn School of Pathology, Oxford, UK.
  • Davis BG; Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.
Science ; 377(6604): eabm3125, 2022 07 22.
Article in English | MEDLINE | ID: covidwho-1901907
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Sialic Acids / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abm3125

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Sialic Acids / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Humans Language: English Journal: Science Year: 2022 Document Type: Article Affiliation country: Science.abm3125