8VQ9
Prefusion stabilized structure of the SARS-CoV-2 fusion machinery
Summary for 8VQ9
| Entry DOI | 10.2210/pdb8vq9/pdb |
| EMDB information | 43435 |
| Descriptor | Spike protein S2, 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 | sarbecoviruses, spike glycoprotein, fusion protein, prefusion-stabilized, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Sarbecovirus |
| Total number of polymer chains | 3 |
| Total formula weight | 210483.04 |
| Authors | Lee, J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2024-01-18, release date: 2024-07-24, Last modification date: 2024-11-20) |
| Primary citation | Lee, J.,Stewart, C.,Schafer, A.,Leaf, E.M.,Park, Y.J.,Asarnow, D.,Powers, J.M.,Treichel, C.,Sprouse, K.R.,Corti, D.,Baric, R.,King, N.P.,Veesler, D. A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines. Nat Commun, 15:5496-5496, 2024 Cited by PubMed Abstract: Evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S subunit, which folds as a spring-loaded fusion machinery. We describe a strategy for prefusion-stabilization and high yield recombinant production of SARS-CoV-2 S trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S subunits. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S trimer elicits broadly reactive sarbecovirus antibodies and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines. PubMed: 38944664DOI: 10.1038/s41467-024-49656-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
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