SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects

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 uncl...

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Veröffentlicht in:Nature structural & molecular biology Jg. 27; H. 8; S. 763 - 767
Hauptverfasser: Wrobel, Antoni G, Benton, Donald J, Xu, Pengqi, Roustan, Chloë, Martin, Stephen R, Rosenthal, Peter B, Skehel, John J, Gamblin, Steven J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Nature Publishing Group 01.08.2020
Schlagworte:
ACE2
Angiotensin-Converting Enzyme 2
Animals
Betacoronavirus - genetics
Betacoronavirus - metabolism
Betacoronavirus - ultrastructure
Binding
Binding Sites
Chiroptera - virology
Cleavage
Coronavirus Infections - virology
COVID-19
Cryoelectron Microscopy
Evolution, Molecular
Furin
Furin - chemistry
Gene Expression
Glycoproteins
HEK293 Cells
Host-Pathogen Interactions - genetics
Humans
Models, Molecular
Pandemics
Peptidyl-Dipeptidase A - chemistry
Peptidyl-Dipeptidase A - genetics
Peptidyl-Dipeptidase A - metabolism
Pneumonia, Viral - virology
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Isoforms - chemistry
Protein Isoforms - genetics
Protein Isoforms - metabolism
Protein Stability
Proteins
Proteolysis
Receptors
Receptors, Virus - chemistry
Receptors, Virus - genetics
Receptors, Virus - metabolism
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - metabolism
Stability
Structural Homology, Protein
Viruses
ISSN:1545-9993, 1545-9985, 1545-9985
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1545-9993
1545-9985
1545-9985
DOI:10.1038/s41594-020-0468-7