7JN5

Crystal structure of SARS-CoV receptor binding domain in complex with human antibody CR3022

Summary for 7JN5

• Entry DOI: 10.2210/pdb7jn5/pdb
• Descriptor: CR3022 heavy chain, CR3022 light chain, Spike glycoprotein, ... (7 entities in total)
• Functional Keywords: sars, coronavirus, antibody, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 74646.52

Authors

Wu, N.C.,Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2020-08-03, release date: 2020-10-28, Last modification date: 2024-10-30)

Primary citation

Wu, N.C.,Yuan, M.,Bangaru, S.,Huang, D.,Zhu, X.,Lee, C.D.,Turner, H.L.,Peng, L.,Yang, L.,Burton, D.R.,Nemazee, D.,Ward, A.B.,Wilson, I.A.
A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody.
Plos Pathog., 16:e1009089-e1009089, 2020

PubMed Abstract: Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses.

PubMed: 33275640
DOI: 10.1371/journal.ppat.1009089

Experimental method

X-RAY DIFFRACTION (2.705 Å)