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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Vydané v:	Nature structural & molecular biology Ročník 27; číslo 8; s. 763 - 767
Hlavní autori:	Wrobel, Antoni G, Benton, Donald J, Xu, Pengqi, Roustan, Chloë, Martin, Stephen R, Rosenthal, Peter B, Skehel, John J, Gamblin, Steven J
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Nature Publishing Group 01.08.2020
Predmet:	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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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1545-9993 1545-9985 1545-9985
DOI:	10.1038/s41594-020-0468-7