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-Structure paper
タイトル | Cross-Neutralization of a SARS-CoV-2 Antibody to a Functionally Conserved Site Is Mediated by Avidity. |
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ジャーナル・号・ページ | Immunity, Vol. 53, Issue 6, Page 1272-11280.e5, Year 2020 |
掲載日 | 2020年12月15日 |
![]() | Hejun Liu / Nicholas C Wu / Meng Yuan / Sandhya Bangaru / Jonathan L Torres / Tom G Caniels / Jelle van Schooten / Xueyong Zhu / Chang-Chun D Lee / Philip J M Brouwer / Marit J van Gils / Rogier W Sanders / Andrew B Ward / Ian A Wilson / ![]() ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) / X線回折 |
解像度 | 2.53 - 31.0 Å |
構造データ | ![]() EMDB-22742: ![]() EMDB-22743: ![]() EMDB-22744: ![]() EMDB-22745: ![]() PDB-7jmw: ![]() PDB-7jmx: |
化合物 | ![]() ChemComp-SO4: ![]() ChemComp-ACT: ![]() ChemComp-HOH: |
由来 |
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![]() | VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / Antibody / Spike / Coronavirus / COVID-19 / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |