8VCR
SARS-CoV-2 Spike S2 bound to Fab 54043-5
Summary for 8VCR
| Entry DOI | 10.2210/pdb8vcr/pdb |
| EMDB information | 43139 |
| Descriptor | Spike protein S2, 54043-5 Fab Heavy Chain, 54043-5 Fab Light Chain, ... (5 entities in total) |
| Functional Keywords | sars-cov-2 spike, s2 subunit, viral fusion, monoclonal antibody, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 9 |
| Total formula weight | 347711.99 |
| Authors | Johnson, N.V.,McLellan, J.S. (deposition date: 2023-12-14, release date: 2024-07-31, Last modification date: 2024-11-27) |
| Primary citation | Johnson, N.V.,Wall, S.C.,Kramer, K.J.,Holt, C.M.,Periasamy, S.,Richardson, S.I.,Manamela, N.P.,Suryadevara, N.,Andreano, E.,Paciello, I.,Pierleoni, G.,Piccini, G.,Huang, Y.,Ge, P.,Allen, J.D.,Uno, N.,Shiakolas, A.R.,Pilewski, K.A.,Nargi, R.S.,Sutton, R.E.,Abu-Shmais, A.A.,Parks, R.,Haynes, B.F.,Carnahan, R.H.,Crowe Jr., J.E.,Montomoli, E.,Rappuoli, R.,Bukreyev, A.,Ross, T.M.,Sautto, G.A.,McLellan, J.S.,Georgiev, I.S. Discovery and characterization of a pan-betacoronavirus S2-binding antibody. Structure, 32:1893-, 2024 Cited by PubMed Abstract: The continued emergence of deadly human coronaviruses from animal reservoirs highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq), we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryoelectron microscopy (cryo-EM) structure of 54043-5 bound to the prefusion S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses in vitro, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit. PubMed: 39326419DOI: 10.1016/j.str.2024.08.022 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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