7S0E

Structure of the SARS-CoV-2 S1 subunit in complex with antibody N-612-004

7S0E の概要

• エントリーDOI: 10.2210/pdb7s0e/pdb
• EMDBエントリー: 24788
• 分子名称: Spike glycoprotein, N-612-004 Fab heavy chain, N-612-004 Light Chain (3 entities in total)
• 機能のキーワード: sars-cov-2, antibody, covid-19, spike glycoprotein, mrna display, antiviral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 189038.48

構造登録者

Barnes, C.O.,Bjorkman, P.J. (登録日: 2021-08-30, 公開日: 2021-10-06, 最終更新日: 2025-06-04)

主引用文献

Tanaka, S.,Olson, C.A.,Barnes, C.O.,Higashide, W.,Gonzalez, M.,Taft, J.,Richardson, A.,Martin-Fernandez, M.,Bogunovic, D.,Gnanapragasam, P.N.P.,Bjorkman, P.J.,Spilman, P.,Niazi, K.,Rabizadeh, S.,Soon-Shiong, P.
Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display.
Cell Rep, 38:110348-110348, 2022

PubMed Abstract: The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.

PubMed: 35114110
DOI: 10.1016/j.celrep.2022.110348

実験手法

ELECTRON MICROSCOPY (4.9 Å)