Journal article
Pathogen-sugar interactions revealed by universal saturation transfer analysis
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.0MB, Terms of use)
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- Publisher copy:
- 10.1126/science.abm3125
Authors
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science More from this journal
- Volume:
- 377
- Issue:
- 6604
- Article number:
- eabm3125
- Publication date:
- 2022-06-23
- Acceptance date:
- 2022-06-16
- DOI:
- EISSN:
-
1095-9203
- ISSN:
-
0036-8075
- Pmid:
-
35737812
- Language:
-
English
- Keywords:
- Pubs id:
-
1265397
- Local pid:
-
pubs:1265397
- Deposit date:
-
2022-07-26
- ARK identifier:
Terms of use
- Copyright holder:
- Buchanan et al.
- Copyright date:
- 2022
- Rights statement:
- ©2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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