| Title: |
Pathogen-sugar interactions revealed by universal saturation transfer analysis |
| Authors: |
GEN-COVID Multicenter Study; Sub NMR Spectroscopy; NMR Spectroscopy |
| Publication Year: |
2022 |
| Subject Terms: |
General |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
0036-8075 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/425815 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/425815 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.13355B46 |
| Database: |
BASE |