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8DT3

Cryo-EM structure of spike binding to Fab of neutralizing antibody (locally refined)

Summary for 8DT3
Entry DOI10.2210/pdb8dt3/pdb
EMDB information27690
DescriptorSpike glycoprotein, Heavy chain Fab of SW186, Light chain Fab of SW186, ... (4 entities in total)
Functional Keywordssars-cov2, antibody, neutralizing, viral protein-immune system complex, viral protein/immune system
Biological sourceSevere acute respiratory syndrome coronavirus 2
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Total number of polymer chains3
Total formula weight192781.59
Authors
Sun, P.C.,Fang, Y.,Bai, X.C.,Chen, Z.J. (deposition date: 2022-07-25, release date: 2022-08-03, Last modification date: 2024-11-06)
Primary citationFang, Y.,Sun, P.,Xie, X.,Du, M.,Du, F.,Ye, J.,Kalveram, B.K.,Plante, J.A.,Plante, K.S.,Li, B.,Bai, X.C.,Shi, P.Y.,Chen, Z.J.
An antibody that neutralizes SARS-CoV-1 and SARS-CoV-2 by binding to a conserved spike epitope outside the receptor binding motif.
Sci Immunol, 7:eabp9962-eabp9962, 2022
Cited by
PubMed Abstract: The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as the Omicron variants that are highly transmissible and immune evasive, underscores the need to develop therapeutic antibodies with broad neutralizing activities. Here, we used the LIBRA-seq technology, which identified SARS-CoV-2-specific B cells via DNA barcoding and subsequently single-cell sequenced BCRs, to identify an antibody, SW186, which could neutralize major SARS-CoV-2 variants of concern, including Beta, Delta, and Omicron, as well as SARS-CoV-1. The cryo-EM structure of SW186 bound to the receptor binding domain (RBD) of the viral spike protein showed that SW186 interacted with an epitope of the RBD that is not at the interface of its binding to the ACE2 receptor but is highly conserved among SARS coronaviruses. This epitope encompasses a glycosylation site (N343) of the viral spike protein. Administration of SW186 in mice after they were infected with SARS-CoV-2 Alpha, Beta, or Delta variants reduced the viral loads in the lung. These results demonstrated that SW186 neutralizes diverse SARS coronaviruses by binding to a conserved RBD epitope, which could serve as a target for further antibody development.
PubMed: 35926067
DOI: 10.1126/sciimmunol.abp9962
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.3 Å)
Structure validation

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