7M6I

Structure of the SARS-CoV-2 S 2P trimer in complex with the human neutralizing antibody Fab fragment, BG1-24

Summary for 7M6I

• Entry DOI: 10.2210/pdb7m6i/pdb
• EMDB information: 23697
• Descriptor: Spike glycoprotein, BG1-24 Fab Heavy Chain, BG1-24 Fab Light Chain, ... (7 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, covid-19, antibody, neutralizing antibody, receptor binding domain, spike glycoprotein, antiviral protein, viral protein-antiviral protein complex, viral protein/antiviral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus); More
• Total number of polymer chains: 7
• Total formula weight: 523136.00

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2021-03-25, release date: 2021-05-05, Last modification date: 2021-06-23)

Primary citation

Scheid, J.F.,Barnes, C.O.,Eraslan, B.,Hudak, A.,Keeffe, J.R.,Cosimi, L.A.,Brown, E.M.,Muecksch, F.,Weisblum, Y.,Zhang, S.,Delorey, T.,Woolley, A.E.,Ghantous, F.,Park, S.M.,Phillips, D.,Tusi, B.,Huey-Tubman, K.E.,Cohen, A.A.,Gnanapragasam, P.N.P.,Rzasa, K.,Hatziioanno, T.,Durney, M.A.,Gu, X.,Tada, T.,Landau, N.R.,West Jr., A.P.,Rozenblatt-Rosen, O.,Seaman, M.S.,Baden, L.R.,Graham, D.B.,Deguine, J.,Bieniasz, P.D.,Regev, A.,Hung, D.,Bjorkman, P.J.,Xavier, R.J.
B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.
Cell, 184:3205-, 2021

PubMed Abstract: Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.

PubMed: 34015271
DOI: 10.1016/j.cell.2021.04.032

Experimental method

ELECTRON MICROSCOPY (4 Å)