6ZGI

Furin Cleaved Spike Protein of SARS-CoV-2 in Closed Conformation

Summary for 6ZGI

• Entry DOI: 10.2210/pdb6zgi/pdb
• EMDB information: 11207
• Descriptor: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: sars-cov-2, spike, virus glycoprotein, coronavirus, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 3
• Total formula weight: 443998.05

Authors

Wrobel, A.G.,Benton, D.J.,Rosenthal, P.B.,Gamblin, S.J. (deposition date: 2020-06-18, release date: 2020-07-01, Last modification date: 2024-11-13)

Primary citation

Wrobel, A.G.,Benton, D.J.,Xu, P.,Roustan, C.,Martin, S.R.,Rosenthal, P.B.,Skehel, J.J.,Gamblin, S.J.
SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
Nat.Struct.Mol.Biol., 27:763-767, 2020

PubMed 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.

PubMed: 32647346
DOI: 10.1038/s41594-020-0468-7

Experimental method

ELECTRON MICROSCOPY (2.9 Å)