7SJS
Crystal structure of SARS-CoV-2 spike stem helix peptide in complex with neutralizing antibody CC40.8
Summary for 7SJS
| Entry DOI | 10.2210/pdb7sjs/pdb |
| Descriptor | CC40.8 Fab heavy chain, CC40.8 Fab light chain, stem helix peptide of Spike protein S2', ... (7 entities in total) |
| Functional Keywords | sars-cov-2, antibody, spike, s2, stem helix, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 49177.54 |
| Authors | Yuan, M.,Wilson, I.A. (deposition date: 2021-10-18, release date: 2022-01-12, Last modification date: 2024-10-23) |
| Primary citation | Zhou, P.,Yuan, M.,Song, G.,Beutler, N.,Shaabani, N.,Huang, D.,He, W.T.,Zhu, X.,Callaghan, S.,Yong, P.,Anzanello, F.,Peng, L.,Ricketts, J.,Parren, M.,Garcia, E.,Rawlings, S.A.,Smith, D.M.,Nemazee, D.,Teijaro, J.R.,Rogers, T.F.,Wilson, I.A.,Burton, D.R.,Andrabi, R. A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection. Sci Transl Med, 14:eabi9215-eabi9215, 2022 Cited by PubMed Abstract: Broadly neutralizing antibodies (bnAbs) to coronaviruses (CoVs) are valuable in their own right as prophylactic and therapeutic reagents to treat diverse CoVs and as templates for rational pan-CoV vaccine design. We recently described a bnAb, CC40.8, from a CoV disease 2019 (COVID-19) convalescent donor that exhibits broad reactivity with human β-CoVs. Here, we showed that CC40.8 targets the conserved S2 stem helix region of the CoV spike fusion machinery. We determined a crystal structure of CC40.8 Fab with a SARS-CoV-2 S2 stem peptide at 1.6-Å resolution and found that the peptide adopted a mainly helical structure. Conserved residues in β-CoVs interacted with CC40.8 antibody, thereby providing a molecular basis for its broad reactivity. CC40.8 exhibited in vivo protective efficacy against SARS-CoV-2 challenge in two animal models. In both models, CC40.8-treated animals exhibited less weight loss and reduced lung viral titers compared to controls. Furthermore, we noted that CC40.8-like bnAbs are relatively rare in human COVID-19 infection, and therefore, their elicitation may require rational structure-based vaccine design strategies. Overall, our study describes a target on β-CoV spike proteins for protective antibodies that may facilitate the development of pan-β-CoV vaccines. PubMed: 35133175DOI: 10.1126/scitranslmed.abi9215 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.612 Å) |
Structure validation
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