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TitleControlling the SARS-CoV-2 spike glycoprotein conformation.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 10, Page 925-933, Year 2020
Publish dateJul 22, 2020
AuthorsRory Henderson / Robert J Edwards / Katayoun Mansouri / Katarzyna Janowska / Victoria Stalls / Sophie M C Gobeil / Megan Kopp / Dapeng Li / Rob Parks / Allen L Hsu / Mario J Borgnia / Barton F Haynes / Priyamvada Acharya /
PubMed AbstractThe coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The ...The coronavirus (CoV) spike (S) protein, involved in viral-host cell fusion, is the primary immunogenic target for virus neutralization and the current focus of many vaccine design efforts. The highly flexible S-protein, with its mobile domains, presents a moving target to the immune system. Here, to better understand S-protein mobility, we implemented a structure-based vector analysis of available β-CoV S-protein structures. Despite an overall similarity in domain organization, we found that S-proteins from different β-CoVs display distinct configurations. Based on this analysis, we developed two soluble ectodomain constructs for the SARS-CoV-2 S-protein, in which the highly immunogenic and mobile receptor binding domain (RBD) is either locked in the all-RBDs 'down' position or adopts 'up' state conformations more readily than the wild-type S-protein. These results demonstrate that the conformation of the S-protein can be controlled via rational design and can provide a framework for the development of engineered CoV S-proteins for vaccine applications.
External linksNat Struct Mol Biol / PubMed:32699321 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 12.06 Å
Structure data

EMDB-21997, PDB-6x29:
SARS-CoV-2 rS2d Down State Spike Protein Trimer
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-21999: SARS-CoV-2 u1S2q 1 Up RBD Spike Protein Trimer
PDB-6x2a: SARS-CoV-2 u1S2q 1-RBD Up Spike Protein Trimer
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-22000: SARS-CoV-2 u1S2q 2 RBD Up Spike Protein Trimer
PDB-6x2b: SARS-CoV-2 u1S2q 2-RBD Up Spike Protein Trimer
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-22001, PDB-6x2c:
SARS-CoV-2 u1S2q All Down RBD State Spike Protein Trimer
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-22809:
SARS-CoV-2 rS2d RBD-Down State Spike Protein Trimer
Method: EM (single particle) / Resolution: 12.06 Å

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN / Trimer

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