8DM4
Cryo-EM structure of SARS-CoV-2 Omicron BA.2 spike protein in complex with Fab 4A8 (focused refinement of NTD and 4A8)
Summary for 8DM4
| Entry DOI | 10.2210/pdb8dm4/pdb |
| EMDB information | 27526 |
| Descriptor | Spike glycoprotein, Fab 4A8 heavy chain, Fab 4A8 light chain, ... (5 entities in total) |
| Functional Keywords | sars-cov-2, glycoprotein, fusion protein, viral protein, viral protein-immune system complex, omicron, ba.2, 4a8, viral protein/immune system |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 3 |
| Total formula weight | 197226.99 |
| Authors | Zhu, X.,Saville, J.W.,Mannar, D.,Berezuk, A.M.,Cholak, S.,Tuttle, K.S.,Vahdatihassani, F.,Subramaniam, S. (deposition date: 2022-07-08, release date: 2023-01-25, Last modification date: 2024-10-16) |
| Primary citation | Saville, J.W.,Mannar, D.,Zhu, X.,Berezuk, A.M.,Cholak, S.,Tuttle, K.S.,Vahdatihassani, F.,Subramaniam, S. Structural analysis of receptor engagement and antigenic drift within the BA.2 spike protein. Cell Rep, 42:111964-111964, 2023 Cited by PubMed Abstract: The BA.2 sub-lineage of the Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant rapidly supplanted the original BA.1 sub-lineage in early 2022. Both lineages threatened the efficacy of vaccine-elicited antibodies and acquired increased binding to several mammalian ACE2 receptors. Cryoelectron microscopy (cryo-EM) analysis of the BA.2 spike (S) glycoprotein in complex with mouse ACE2 (mACE2) identifies BA.1- and BA.2-mutated residues Q493R, N501Y, and Y505H as complementing non-conserved residues between human and mouse ACE2, rationalizing the enhanced S protein-mACE2 interaction for Omicron variants. Cryo-EM structures of the BA.2 S-human ACE2 complex and of the extensively mutated BA.2 amino-terminal domain (NTD) reveal a dramatic reorganization of the highly antigenic N1 loop into a β-strand, providing an explanation for decreased binding of the BA.2 S protein to antibodies isolated from BA.1-convalescent patients. Our analysis reveals structural mechanisms underlying the antigenic drift in the rapidly evolving Omicron variant landscape. PubMed: 36640338DOI: 10.1016/j.celrep.2022.111964 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.45 Å) |
Structure validation
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