ArticleNature communications2025
Human coronavirus HKU1 spike structures reveal the basis for sialoglycan specificity and carbohydrate-promoted conformational changes.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Aminopeptidase N is a receptor for hedgehog merbecoviruses.Nature microbiology · 2026Article
- Targeting virus-glycan recognition in influenza viruses and coronaviruses: from the molecular principles to glycomimetic antivirals strategies.RSC chemical biology · 2026Review
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- OC43 clinical isolate spike proteins have distinct carbohydrate-binding properties.Nature communications · 2026Article
- Establishment of a human coronavirus HKU1 infection evaluation system using apical-out airway organoids.The Journal of general virology · 2026Article
- Mutations to the HCoV-229E spike have counterbalancing effects on serum antibody neutralization and receptor binding.bioRxiv : the preprint server for biology · 2026Article
- The Enigmatic Conserved Q134-F135-N137 Triad in SARS-CoV-2 Spike Protein: A Conformational Transducer?Biomolecules · 2026Review
- An integrated workflow for structural virology with a 100 keV electron microscope.bioRxiv : the preprint server for biology · 2025Article
- Current Status and Challenges of Vaccine Development for Seasonal Human Coronaviruses.Vaccines · 2025Review
- Human coronavirus HKU1 neutralization by glycan receptor mimicry.bioRxiv : the preprint server for biology · 2025Article
- Dipeptidase 1 is a functional receptor for a porcine coronavirus.Nature microbiology · 2025Article
- Virion motility of sialoglycan-cleaving respiratory viruses.Npj viruses · 2025Review
- Article
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12 authors.
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Abstract
The human coronavirus HKU1 uses both sialoglycoconjugates and the protein transmembrane serine protease 2 (TMPRSS2) as receptors. Carbohydrate binding leads to the spike protein up conformation required for TMPRSS2 binding, an outcome suggesting a distinct mechanism for driving fusion of the viral and host cell membranes. Nevertheless, the conformational changes promoted by carbohydrate binding have not been fully elucidated and the basis for HKU1's carbohydrate binding specificity remains unknown. Reported here are high resolution cryo-EM structures of the HKU1 spike protein trimer in its apo form and in complex with the carbohydrate moiety of a candidate carbohydrate receptor, the 9-O-acetylated GD3 ganglioside. The structures show that the spike monomer can exist in four discrete conformational states and that progression through them would promote the up conformation upon carbohydrate binding. We also show that a six-amino-acid insert is a determinant of HKU1's specificity for gangliosides containing a 9-O-acetylated α2-8-linked disialic acid moiety and that HKU1 shows weak affinity for the 9-O-acetylated sialic acids found on decoy receptors such as mucins.
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