Pathogen-sugar interactions revealed by universal saturation transfer analysis
Authors
- C.J. Buchanan
- B. Gaunt
- P.J. Harrison
- Y. Yang
- J. Liu
- A. Khan
- A.M. Giltrap
- A. Le Bas
- P.N. Ward
- K. Gupta
- M. Dumoux
- T.K. Tan
- L. Schimaski
- S. Daga
- N. Picchiotti
- M. Baldassarri
- E. Benetti
- C. Fallerini
- F. Fava
- A. Giliberti
- P.I. Koukos
- M.J. Davy
- A. Lakshminarayanan
- X. Xue
- G. Papadakis
- L.P. Deimel
- V. Casablancas-Antràs
- T.D.W. Claridge
- A.M.J.J. Bonvin
- Q.J. Sattentau
- S. Furini
- M. Gori
- J. Huo
- R.J. Owens
- C. Schaffitzel
- I. Berger
- A. Renieri
- J.H. Naismith
- A.J. Baldwin
- B.G. Davis
Journal
- Science
Citation
- Science 377 (6604): eabm3125
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.