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TitleSARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 8, Page 763-767, Year 2020
Publish dateJul 9, 2020
AuthorsAntoni G Wrobel / Donald J Benton / Pengqi Xu / Chloë Roustan / Stephen R Martin / Peter B Rosenthal / John J Skehel / Steven J Gamblin /
PubMed AbstractSARS-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 ...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.
External linksNat Struct Mol Biol / PubMed:32647346 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 6.8 Å
Structure data

11203

6zge

EMDB-11203, PDB-6zge:
Uncleavable Spike Protein of SARS-CoV-2 in Closed Conformation
Method: EM (single particle) / Resolution: 2.6 Å

11204

6zgf

EMDB-11204, PDB-6zgf:
Spike Protein of RaTG13 Bat Coronavirus in Closed Conformation
Method: EM (single particle) / Resolution: 3.1 Å

11205

6zgg

EMDB-11205, PDB-6zgg:
Furin Cleaved Spike Protein of SARS-CoV-2 with One RBD Erect
Method: EM (single particle) / Resolution: 3.8 Å

11206

6zgh

EMDB-11206, PDB-6zgh:
Furin Cleaved Spike Protein of SARS-CoV-2 in Intermediate Conformation
Method: EM (single particle) / Resolution: 6.8 Å

11207

6zgi

EMDB-11207, PDB-6zgi:
Furin Cleaved Spike Protein of SARS-CoV-2 in Closed Conformation
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • severe acute respiratory syndrome coronavirus 2
  • bat coronavirus ratg13
KeywordsVIRAL PROTEIN / SARS-CoV-2 / Spike / Virus Glycoprotein / Coronavirus

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