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Cryo-EM structure of coronavirus-HKU1 haemagglutinin esterase reveals architectural changes arising from prolonged circulation in humans.

Daniel L Hurdiss1,2 Ieva Drulyte3 Yifei Lang4 Tatiana M Shamorkina5 Matti F Pronker5 Frank J M van Kuppeveld4 Joost Snijder5 Raoul J de Groot6
Affiliations 6 institutions
  1. Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CH, Utrecht, The Netherlands. [email protected].
  2. Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. [email protected].
  3. Materials and Structural Analysis, Thermo Fisher Scientific, Achtseweg Noord 5, Eindhoven, 5651 GG, The Netherlands.
  4. Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CH, Utrecht, The Netherlands.
  5. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
  6. Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CH, Utrecht, The Netherlands. [email protected].
PMID 32938911 2020 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

The human betacoronaviruses HKU1 and OC43 (subgenus Embecovirus) arose from separate zoonotic introductions, OC43 relatively recently and HKU1 apparently much longer ago. Embecovirus particles contain two surface projections called spike (S) and haemagglutinin-esterase (HE), with S mediating receptor binding and membrane fusion, and HE acting as a receptor-destroying enzyme. Together, they promote dynamic virion attachment to glycan-based receptors, specifically 9-O-acetylated sialic acid. Here we present the cryo-EM structure of the ~80 kDa, heavily glycosylated HKU1 HE at 3.4 Å resolution. Comparison with existing HE structures reveals a drastically truncated lectin domain, incompatible with sialic acid binding, but with the structure and function of the esterase domain left intact. Cryo-EM and mass spectrometry analysis reveals a putative glycan shield on the now redundant lectin domain. The findings further our insight into the evolution and host adaptation of human embecoviruses, and demonstrate the utility of cryo-EM for studying small, heavily glycosylated proteins.

Betacoronavirus Binding Sites Catalytic Domain Coronavirus Infections Cryoelectron Microscopy Glycosylation HEK293 Cells Hemagglutinins, Viral Humans Lectins Mass Spectrometry Models, Molecular N-Acetylneuraminic Acid Polysaccharides Protein Domains Viral Fusion Proteins hemagglutinin esterase

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.80
Key finding

Structural comparison of HKU1 haemagglutinin esterase with related Embecoviruses shows truncation of the lectin domain, reflecting molecular evolution during human host adaptation.

Virus
HCoV-HKU1
Location
Not specified
Supporting text

Here we present the cryo-EM structure of the ~80 kDa, heavily glycosylated HKU1 HE at 3.4 Å resolution. Comparison with existing HE structures reveals a drastically truncated lectin domain, incompatible with sialic acid binding, but with the structure and function of the esterase domain left intact.

Genes or proteins
haemagglutinin esterase
Analysis methods
cryo-EM structural analysis; comparative structural analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The HKU1 haemagglutinin esterase exhibits truncation of the lectin domain and acquisition of a glycan shield, representing molecular adaptation of this coronavirus to sustained human circulation.

Virus
Embecovirus
Host
Not specified
Location
Not specified
Supporting text

Comparison with existing HE structures reveals a drastically truncated lectin domain, incompatible with sialic acid binding, but with the structure and function of the esterase domain left intact. Cryo-EM and mass spectrometry analysis reveals a putative glycan shield on the now redundant lectin domain. The findings further our insight into the evolution and host adaptation of human embecoviruses.

Genes or proteins
haemagglutinin esterase; lectin domain; esterase domain
Receptors
sialic acid
Mechanism types
receptor_binding; immune_escape; host_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.85
Key finding

The HKU1 haemagglutinin esterase has lost compatibility with 9-O-acetylated sialic acid receptor binding due to truncation of its lectin domain while retaining esterase activity.

Virus
Embecovirus
Location
Not specified
Supporting text

Comparison with existing HE structures reveals a drastically truncated lectin domain, incompatible with sialic acid binding, but with the structure and function of the esterase domain left intact.

Method
cryo-EM structure analysis; mass spectrometry
Receptors
9-O-acetylated sialic acid