7JMW

Crystal structure of SARS-CoV-2 spike protein receptor-binding domain in complex with cross-neutralizing antibody COVA1-16 Fab

Summary for 7JMW

• Entry DOI: 10.2210/pdb7jmw/pdb
• Descriptor: Spike protein S1, COVA1-16 heavy chain, COVA1-16 light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, antibody, spike, coronavirus, covid-19, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 3
• Total formula weight: 75864.49

Authors

Liu, H.,Yuan, M.,Zhu, X.,Wu, N.C.,Wilson, I.A. (deposition date: 2020-08-03, release date: 2020-10-14, Last modification date: 2024-10-23)

Primary citation

Liu, H.,Wu, N.C.,Yuan, M.,Bangaru, S.,Torres, J.L.,Caniels, T.G.,van Schooten, J.,Zhu, X.,Lee, C.D.,Brouwer, P.J.M.,van Gils, M.J.,Sanders, R.W.,Ward, A.B.,Wilson, I.A.
Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity.
Immunity, 53:1272-1280.e5, 2020

PubMed Abstract: Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined a crystal structure of the COVA1-16 antibody fragment (Fab) with the SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions with the spike glycoprotein trimer to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long complementarity-determining region (CDR) H3, and competes with the angiotensin-converting enzyme 2 (ACE2) receptor because of steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with the structural and functional rationale for epitope conservation, provide insights for development of more universal SARS-like coronavirus vaccines and therapies.

PubMed: 33242394
DOI: 10.1016/j.immuni.2020.10.023

Experimental method

X-RAY DIFFRACTION (2.89 Å)