7S3N

SARS-CoV-2 S stem helix peptide bound to Fab22

Summary for 7S3N

• Entry DOI: 10.2210/pdb7s3n/pdb
• Descriptor: Spike glycoprotein, Fab22 Heavy Chain, Fab22 Light Chain, ... (4 entities in total)
• Functional Keywords: spike, fusion, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 50018.88

Authors

Goldsmith, J.A.,McLellan, J.S. (deposition date: 2021-09-07, release date: 2021-10-27, Last modification date: 2023-10-18)

Primary citation

Hsieh, C.L.,Werner, A.P.,Leist, S.R.,Stevens, L.J.,Falconer, E.,Goldsmith, J.A.,Chou, C.W.,Abiona, O.M.,West, A.,Westendorf, K.,Muthuraman, K.,Fritch, E.J.,Dinnon 3rd, K.H.,Schafer, A.,Denison, M.R.,Chappell, J.D.,Baric, R.S.,Graham, B.S.,Corbett, K.S.,McLellan, J.S.
Stabilized coronavirus spike stem elicits a broadly protective antibody.
Cell Rep, 37:109929-109929, 2021

PubMed Abstract: Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies.

PubMed: 34710354
DOI: 10.1016/j.celrep.2021.109929

Experimental method

X-RAY DIFFRACTION (1.9 Å)