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

Summary for 7BEO

• Entry DOI: 10.2210/pdb7beo/pdb
• Related: 7EBH 7EBI 7EBJ 7EBK 7EBL 7EBM 7EBN
• Descriptor: Spike glycoprotein, CHLORIDE ION, COVOX-253H55L heavy chain, ... (10 entities in total)
• Functional Keywords: 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
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 10
• Total formula weight: 246039.97

Authors

Zhou, D.,Zhao, Y.,Ren, J.,Stuart, D. (deposition date: 2020-12-24, release date: 2021-03-03, Last modification date: 2024-01-31)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.19 Å)