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SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
Nat Struct Mol Biol. 2020 08; 27(8):763-767.NS

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.

Authors+Show Affiliations

Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. antoni.wrobel@crick.ac.uk.Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. donald.benton@crick.ac.uk.Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. Precision Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.Structural Biology Science Technology Platform, Francis Crick Institute, London, UK.Structural Biology Science Technology Platform, Francis Crick Institute, London, UK.Structural Biology of Cells and Viruses Laboratory, Francis Crick Institute, London, UK.Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK.Structural Biology of Disease Processes Laboratory, Francis Crick Institute, London, UK. steven.gamblin@crick.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32647346

Citation

Wrobel, Antoni G., et al. "SARS-CoV-2 and Bat RaTG13 Spike Glycoprotein Structures Inform On Virus Evolution and Furin-cleavage Effects." Nature Structural & Molecular Biology, vol. 27, no. 8, 2020, pp. 763-767.
Wrobel AG, Benton DJ, Xu P, et al. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat Struct Mol Biol. 2020;27(8):763-767.
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020). SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nature Structural & Molecular Biology, 27(8), 763-767. https://doi.org/10.1038/s41594-020-0468-7
Wrobel AG, et al. SARS-CoV-2 and Bat RaTG13 Spike Glycoprotein Structures Inform On Virus Evolution and Furin-cleavage Effects. Nat Struct Mol Biol. 2020;27(8):763-767. PubMed PMID: 32647346.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. AU - Wrobel,Antoni G, AU - Benton,Donald J, AU - Xu,Pengqi, AU - Roustan,Chloë, AU - Martin,Stephen R, AU - Rosenthal,Peter B, AU - Skehel,John J, AU - Gamblin,Steven J, Y1 - 2020/07/09/ PY - 2020/06/13/received PY - 2020/06/24/accepted PY - 2020/7/11/pubmed PY - 2020/8/28/medline PY - 2020/7/11/entrez SP - 763 EP - 767 JF - Nature structural & molecular biology JO - Nat Struct Mol Biol VL - 27 IS - 8 N2 - 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. SN - 1545-9985 UR - https://www.unboundmedicine.com/medline/citation/32647346/SARS_CoV_2_and_bat_RaTG13_spike_glycoprotein_structures_inform_on_virus_evolution_and_furin_cleavage_effects_ L2 - https://doi.org/10.1038/s41594-020-0468-7 DB - PRIME DP - Unbound Medicine ER -