Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry.
Animals
Carcinoembryonic Antigen
/ chemistry
Cell Line, Tumor
Cryoelectron Microscopy
HEK293 Cells
Humans
Membrane Fusion
Mice
Models, Molecular
Murine hepatitis virus
/ chemistry
Protein Binding
Protein Conformation
Protein Conformation, alpha-Helical
Protein Domains
Protein Multimerization
Proteolysis
Receptors, Virus
/ chemistry
Recombinant Proteins
/ chemistry
Severe acute respiratory syndrome-related coronavirus
/ chemistry
Spike Glycoprotein, Coronavirus
/ chemistry
Virus Attachment
Virus Internalization
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
23
10
2019
accepted:
08
02
2020
revised:
19
03
2020
pubmed:
10
3
2020
medline:
26
3
2020
entrez:
10
3
2020
Statut:
epublish
Résumé
Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses.
Identifiants
pubmed: 32150576
doi: 10.1371/journal.ppat.1008392
pii: PPATHOGENS-D-19-01992
pmc: PMC7082060
doi:
Substances chimiques
Carcinoembryonic Antigen
0
Ceacam1 protein, mouse
0
Receptors, Virus
0
Recombinant Proteins
0
Spike Glycoprotein, Coronavirus
0
spike glycoprotein, SARS-CoV
0
spike protein, mouse hepatitis virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008392Subventions
Organisme : NIAID NIH HHS
ID : R01 AI089728
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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