Pathogen-sugar interactions revealed by universal saturation transfer analysis

DOI: 10.1126/science.abm3125

Authors: Charles J. Buchanan (University of Oxford) , Ben Gaunt (Rosalind Franklin Institute) , Peter J. Harrison (Wellcome Centre for Human Genetics, University of Oxford; Diamond Light Source) , Yun Yang (Rosalind Franklin Institute; Wellcome Centre for Human Genetics, University of Oxford) , Jiwei Liu (Rosalind Franklin Institute) , Aziz Khan (University of Oxford; Rosalind Franklin Institute) , Andrew M. Giltrap (University of Oxford; Rosalind Franklin Institute) , Audrey Le Bas (Rosalind Franklin Institute; The Wellcome Centre for Human Genetics, University of Oxford; Protein Production UK) , Philip N. Ward (Wellcome Centre for Human Genetics, University of Oxford) , Kapil Gupta (University of Bristol) , Maud Dumoux (Diamond Light Source) , Tiong Kit Tan (University of Oxford) , Lisa Schimaski (University of Oxford, John Radcliffe Hospital) , Sergio Daga (University of Siena) , Nicola Picchiotti (University of Siena) , Margherita Baldassarri (University of Siena) , Elisa Benetti (University of Siena) , Chiara Fallerini (University of Siena) , Francesca Fava (University of Siena) , Annarita Giliberti (University of Siena) , Panagiotis I. Koukos (Utrecht University) , Matthew J. Davy (Rosalind Franklin Institute) , Abirami Lakshminarayanan (University of Oxford; Rosalind Franklin Institute) , Xiaochao Xue (University of Oxford) , Georgios Papadakis (University of Oxford) , Lachlan P. Deimel (University of Oxford) , Virgínia Casablancas-Antràs (University of Oxford; Maasai, I3S CNRS, Université Côte d’Azur) , Timothy D. W. Claridge (University of Oxford) , Alexandre M. J. J. Bonvin (Utrecht University) , Quentin J. Sattentau (University of Oxford) , Simone Furini (University of Siena) , Marco Gori (University of Siena) , Jiandong Huo (Rosalind Franklin Institute; Wellcome Centre for Human Genetics, University of Oxford) , Raymond J. Owens (Rosalind Franklin Institute; Wellcome Centre for Human Genetics, University of Oxford) , Christiane Schaffitzel (University of Bristol) , Imre Berger (University of Bristol) , Alessandra Renieri (University of Siena; Genetica Medica) , James H. Naismith (Rosalind Franklin Institute; Wellcome Centre for Human Genetics, University of Oxford) , Andrew J. Baldwin (University of Oxford; Rosalind Franklin Institute) , Benjamin G. Davis (University of Oxford; Rosalind Franklin Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 479

State: Published (Approved)
Published: June 2022

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 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.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Membrane Protein Laboratory (MPL)
Instruments: NONE-No attached Diamond beamline

Added On: 27/06/2022 13:43

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags: