Pathogen-sugar interactions revealed by universal saturation transfer analysis.
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.
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
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