Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies.

Autor: Nan X; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China.; State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China., Li Y; Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China., Zhang R; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China.; Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China., Wang R; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China.; Tsinghua-Peking Joint Center for Life Sciences, Beijing, China., Lv N; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China.; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing, China., Li J; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Chen Y; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China.; University of Chinese Academy of Sciences, Beijing, China., Zhou B; Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China., Wang Y; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China., Wang Z; The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China., Zhu J; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China., Chen J; The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China., Li J; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China., Chen W; State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing, China., Zhang Q; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China., Shi X; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China., Zhao C; State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, China., Chen C; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China., Liu Z; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhao Y; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China.; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing, China., Liu D; Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, China., Wang X; The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China., Yan LT; State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing, China., Li T; Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. litsh@263.net.; State Key Laboratory for Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Beijing, China. litsh@263.net.; Center for AIDS Research, Chinese Academy of Medical Sciences, Beijing, China. litsh@263.net., Zhang L; Comprehensive AlDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University, Beijing, China. zhanglinqi@tsinghua.edu.cn.; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China. zhanglinqi@tsinghua.edu.cn.; Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, China. zhanglinqi@tsinghua.edu.cn., Yang YR; CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, National Center for Nanoscience and Technology, Beijing, China. yangyh@nanoctr.cn.; University of Chinese Academy of Sciences, Beijing, China. yangyh@nanoctr.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Dec 04; Vol. 15 (1), pp. 10578. Date of Electronic Publication: 2024 Dec 04.
DOI: 10.1038/s41467-024-54746-5
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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