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| Title | Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies. |
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| Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 10578, Year 2024 |
| Publish date | Dec 4, 2024 |
 Authors | Xuanyu Nan / Yujie Li / Rui Zhang / Ruoke Wang / Niannian Lv / Jiayi Li / Yuanfang Chen / Bini Zhou / Yangjunqi Wang / Ziyi Wang / Jiayi Zhu / Jing Chen / Jinqian Li / Wenlong Chen / Qi Zhang / Xuanling Shi / Changwen Zhao / Chunying Chen / Zhihua Liu / Yuliang Zhao / Dongsheng Liu / Xinquan Wang / Li-Tang Yan / Taisheng Li / Linqi Zhang / Yuhe R Yang /  |
| PubMed Abstract | The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their ...The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its Omicron subvariants drastically amplifies transmissibility, infectivity, and immune escape, mainly due to their resistance to most neutralizing antibodies. Thus, exploring the mechanisms underlying antibody evasion is crucial. Although the full-length native form of antibody, immunoglobulin G (IgG), offers valuable insights into the neutralization, structural investigations primarily focus on the fragment of antigen-binding (Fab). Here, we employ single-particle cryo-electron microscopy (cryo-EM) to characterize a W328-6H2 antibody, in its native IgG form complexed with severe acute respiratory syndrome (SARS), severe acute respiratory syndrome coronavirus 2 wild-type (WT) and Omicron variant BA.1 spike protein (S). Three high-resolution structures reveal that the full-length IgG forms a centered head-to-head dimer of trimer when binds fully stoichiometrically with both SARS and WT S, while adopting a distinct offset configuration with Omicron BA.1 S. Combined with functional assays, our results suggest that, beyond the binding affinity between the RBD epitope and Fab, the higher-order architectures of S trimer and full-length IgG play an additional role in neutralization, enriching our understanding of enhanced neutralization by SARS-CoV-2 antibodies. |
 External links | Nat Commun / PubMed:39632831 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.55 - 25.0 Å |
| Structure data |  EMDB-35953: Immune complex of W328-6H2 Fab binding the RBD of SARS-CoV-1 2p spike protein  EMDB-35961: Immune complex of W328-6H2 Fab binding the RBD of SARS-CoV-2 WT 6p spike protein  EMDB-35962: Immune complex of W328-6H2 Fab binding the RBD of Omicron BA.1 6p spike protein added BS3 crosslinker  EMDB-35963: Immune complex of W328-6H2 IgG binding the RBD of Omicron BA.1 6p spike protein  EMDB-35970: Human ACE2 binding the complex of Omicron BA.1 6p spike protein and W328-6H2 IgG  EMDB-35986: Cryo-EM structure of SARS-CoV-1 2p spike protein in complex with W328-6H2 IgG  EMDB-35995: Cryo-EM structure of SARS-CoV-2 WT 6p spike protein in complex with W328-6H2 IgG  EMDB-36058: Cryo-EM structure of Omicron BA.1 6p spike protein in complex with W328-6H2 IgG EMDB-36113: Cryo-EM structure of SARS-CoV-1 2p RBD in complex with W328-6H2(local refinement) EMDB-36121, PDB-8jap: EMDB-36122, PDB-8jam:  EMDB-36257: Immune complex of W328-6H2 IgG binding the RBD of SARS-CoV-1 2p spike protein  EMDB-36267: Immune complex of W328-6H2 IgG binding the RBD of SARS-CoV-2 WT 6p spike protein |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords | VIRAL PROTEIN / Cryo-EM / Complex / SARS-CoV-1 / antibody / Homo sapiens / IgG / RBD / local refinement / Omicron BA.1 / SARS-CoV-2 |
homo sapiens (human)
Severe acute respiratory syndrome coronavirus
severe acute respiratory syndrome coronavirus 2
severe acute respiratory syndrome-related coronavirus