7AKJ

Structure of the SARS-CoV spike glycoprotein in complex with the 47D11 neutralizing antibody Fab fragment

7AKJ の概要

• エントリーDOI: 10.2210/pdb7akj/pdb
• EMDBエントリー: 11813
• 分子名称: Spike glycoprotein, 47D11 neutralizing antibody heavy chain, 47D11 neutralizing antibody light chain, ... (7 entities in total)
• 機能のキーワード: sars-cov, spike, neutralizing antibody, viral protein
• 由来する生物種: SARS coronavirus WH20; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 489975.40

構造登録者

Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Howes, S.C.,van Kuppeveld, F.J.M.,Foerster, F.,Bosch, B.J. (登録日: 2020-10-01, 公開日: 2021-05-19, 最終更新日: 2021-06-16)

主引用文献

Fedry, J.,Hurdiss, D.L.,Wang, C.,Li, W.,Obal, G.,Drulyte, I.,Du, W.,Howes, S.C.,van Kuppeveld, F.J.M.,Forster, F.,Bosch, B.J.
Structural insights into the cross-neutralization of SARS-CoV and SARS-CoV-2 by the human monoclonal antibody 47D11.
Sci Adv, 7:-, 2021

PubMed Abstract: The emergence of SARS-CoV-2 antibody escape mutations highlights the urgent need for broadly neutralizing therapeutics. We previously identified a human monoclonal antibody, 47D11, capable of cross-neutralizing SARS-CoV-2 and SARS-CoV and protecting against the associated respiratory disease in an animal model. Here, we report cryo-EM structures of both trimeric spike ectodomains in complex with the 47D11 Fab. 47D11 binds to the closed receptor-binding domain, distal to the ACE2 binding site. The CDRL3 stabilizes the N343 glycan in an upright conformation, exposing a mutationally constrained hydrophobic pocket, into which the CDRH3 loop inserts two aromatic residues. 47D11 stabilizes a partially open conformation of the SARS-CoV-2 spike, suggesting that it could be used effectively in combination with other antibodies targeting the exposed receptor-binding motif. Together, these results reveal a cross-protective epitope on the SARS-CoV-2 spike and provide a structural roadmap for the development of 47D11 as a prophylactic or postexposure therapy for COVID-19.

PubMed: 33958322
DOI: 10.1126/sciadv.abf5632

実験手法

ELECTRON MICROSCOPY (3.8 Å)