Pathogen-sugar interactions revealed by universal saturation transfer analysis.
Charles J BuchananBenjamin GauntPeter J HarrisonYun YangJiwei LiuAziz KhanAndrew M GiltrapAudrey Le BasPhilip N WardKapil GuptaMaud DumouxTiong Kit TanLisa SchimaskiSergio DagaNicola PicchiottiMargherita BaldassarriElisa BenettiChiara FalleriniFrancesca FavaAnnarita GilibertiPanagiotis I KoukosMatthew J DavyAbirami LakshminarayananXiaochao XueGeorgios PapadakisLachlan P DeimelVirgínia Casablancas-AntràsTimothy D W ClaridgeAlexandre M J J BonvinQuentin J SattentauSimone FuriniMarco GoriJiandong HuoRaymond J OwensChristiane SchaffitzelImre BergerAlessandra Renierinull nullJames H NaismithAndrew J BaldwinBenjamin G DavisPublished in: Science (New York, N.Y.) (2022)
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.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- cell surface
- high resolution
- coronavirus disease
- electron microscopy
- binding protein
- dna binding
- escherichia coli
- copy number
- antimicrobial resistance
- pseudomonas aeruginosa
- candida albicans
- case report
- mass spectrometry
- dna methylation
- single cell
- gram negative
- electronic health record
- transcription factor
- protein protein