The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects
Open accessPublished version of a preprint
Abstract
SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.
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“Consequently, a loss-of-function modification or deletion of the furin cleavage site of the S protein in vaccine development can be beneficial.70,71”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [71]
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Metadata
- Authors
- Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J.
- Affiliations
- The Francis Crick Institute (GB)
- Sun Yat-sen University (CN)
- Corresponding author
- Wrobel, Antoni G.
- Benton, Donald J.
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2020-07-09
- Volume
- 27
- Issue
- 8
- Pages
- 763-767
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC7610980
- OpenAlex
- W3040801746
- Cited by
- 544
- References
- 37
- Citations by year
- 2026: 20 · 2025: 30 · 2024: 53 · 2023: 82 · 2022: 129 · 2021: 180 · 2020: 48
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-08-26)
- Open access
- bronze
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK (FC001078, FC001143)
- Wellcome Trust (FC001078, FC001143)
- RCUK | Medical Research Council (FC001078, FC001143)
- Sun Yat-sen University
- 100 Top Talents Program of Sun Yat-sen University & the Sanming Project of Medicine in Shenzhen
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- SARS-CoV-2, RaTG13, spike protein, furin cleavage, ACE2 binding, protein stability, bat coronaviruses, viral evolution, SARS-CoV-2 origin, receptor binding affinity
- MeSH terms
- Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Animals, Binding Sites, Chiroptera, Humans, Peptidyl-Dipeptidase A, Models, Molecular, Pneumonia, Viral, Protein Binding, Receptors, Virus, Recombinant Proteins, Gene Expression, Coronavirus Infections, Evolution, Molecular, Protein Isoforms, Cryoelectron Microscopy, Structural Homology, Protein, Furin, Protein Interaction Domains and Motifs, Host-Pathogen Interactions, Protein Stability, HEK293 Cells, Pandemics, Proteolysis, Spike Glycoprotein, Coronavirus
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