7JMX

Crystal structure of a SARS-CoV-2 cross-neutralizing antibody COVA1-16 Fab

7JMX の概要

• エントリーDOI: 10.2210/pdb7jmx/pdb
• 分子名称: COVA1-16 heavy chain, COVA1-16 light chain, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, antibody, spike, coronavirus, covid-19, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49691.97

構造登録者

Liu, H.,Yuan, M.,Zhu, X.,Wu, N.C.,Wilson, I.A. (登録日: 2020-08-03, 公開日: 2020-10-14, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.53 Å)