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-Structure paper
Title | Controlling the SARS-CoV-2 spike glycoprotein conformation. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 27, Issue 10, Page 925-933, Year 2020 |
Publish date | Jul 22, 2020 |
Authors | Rory 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 Abstract | 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 ...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 links | Nat Struct Mol Biol / PubMed:32699321 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.7 - 12.06 Å |
Structure data | EMDB-21997, PDB-6x29: EMDB-21999: SARS-CoV-2 u1S2q 1 Up RBD Spike Protein Trimer EMDB-22000: SARS-CoV-2 u1S2q 2 RBD Up Spike Protein Trimer EMDB-22001, PDB-6x2c: EMDB-22809: |
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Keywords | VIRAL PROTEIN / Trimer |