7BEO

Crystal structure of the receptor binding domain of SARS-CoV-2 Spike glycoprotein in a ternary complex with COVOX-253H55L and COVOX-75 Fabs

7BEO の概要

• エントリーDOI: 10.2210/pdb7beo/pdb
• 関連するPDBエントリー: 7EBH 7EBI 7EBJ 7EBK 7EBL 7EBM 7EBN
• 分子名称: Spike glycoprotein, CHLORIDE ION, COVOX-253H55L heavy chain, ... (10 entities in total)
• 機能のキーワード: sars-cov-2, antibody, germline, v-gene, receptor-binding-domain, spike, neutralisation, protection, glycosylation, valency, viral protein/immune system, viral protein, immune system, viral protein-immune system complex
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 246039.97

構造登録者

Zhou, D.,Zhao, Y.,Ren, J.,Stuart, D. (登録日: 2020-12-24, 公開日: 2021-03-03, 最終更新日: 2024-11-20)

主引用文献

Dejnirattisai, W.,Zhou, D.,Ginn, H.M.,Duyvesteyn, H.M.E.,Supasa, P.,Case, J.B.,Zhao, Y.,Walter, T.S.,Mentzer, A.J.,Liu, C.,Wang, B.,Paesen, G.C.,Slon-Campos, J.,Lopez-Camacho, C.,Kafai, N.M.,Bailey, A.L.,Chen, R.E.,Ying, B.,Thompson, C.,Bolton, J.,Fyfe, A.,Gupta, S.,Tan, T.K.,Gilbert-Jaramillo, J.,James, W.,Knight, M.,Carroll, M.W.,Skelly, D.,Dold, C.,Peng, Y.,Levin, R.,Dong, T.,Pollard, A.J.,Knight, J.C.,Klenerman, P.,Temperton, N.,Hall, D.R.,Williams, M.A.,Paterson, N.G.,Bertram, F.K.R.,Siebert, C.A.,Clare, D.K.,Howe, A.,Radecke, J.,Song, Y.,Townsend, A.R.,Huang, K.A.,Fry, E.E.,Mongkolsapaya, J.,Diamond, M.S.,Ren, J.,Stuart, D.I.,Screaton, G.R.
The antigenic anatomy of SARS-CoV-2 receptor binding domain.
Cell, 184:2183-, 2021

PubMed Abstract: Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC < 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

PubMed: 33756110
DOI: 10.1016/j.cell.2021.02.032

実験手法

X-RAY DIFFRACTION (3.19 Å)