A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV
Top Cited Papers
Open Access
- 8 May 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 368 (6491), 630-633
- https://doi.org/10.1126/science.abb7269
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the “up” conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.Keywords
Funding Information
- National Institute of Allergy and Infectious Diseases (K99 AI139445)
- Bill and Melinda Gates Foundation (OPP1170236)
- National Natural Science Foundation of China (N_HKU737/18)
- Institut Pasteur (Calmette and Yersin scholarship)
This publication has 46 references indexed in Scilit:
- IgBLAST: an immunoglobulin variable domain sequence analysis toolNucleic Acids Research, 2013
- A Highly Conserved Neutralizing Epitope on Group 2 Influenza A VirusesScience, 2011
- PHENIX: a comprehensive Python-based system for macromolecular structure solutionActa crystallographica. Section D, Structural biology, 2010
- Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding DomainJournal of Molecular Biology, 2009
- Inference of Macromolecular Assemblies from Crystalline StateJournal of Molecular Biology, 2007
- Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape MutantsPLoS Medicine, 2006
- The SWISS-MODEL workspace: a web-based environment for protein structure homology modellingBioinformatics, 2005
- Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome CoronavirusJournal of Virology, 2005
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997