8SMI

Crystal structure of antibody WRAIR-2123 in complex with SARS-CoV-2 receptor binding domain

Summary for 8SMI

• Entry DOI: 10.2210/pdb8smi/pdb
• Descriptor: Spike protein S1, WRAIR-2123 Fab heavy chain, WRAIR-2123 Fab light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, antibody, immune system, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV, COVID-19 virus); More
• Total number of polymer chains: 3
• Total formula weight: 71360.56

Authors

Sankhala, R.S.,Jensen, J.L.,Joyce, M.G. (deposition date: 2023-04-26, release date: 2023-12-13, Last modification date: 2024-10-30)

Primary citation

Sankhala, R.S.,Dussupt, V.,Chen, W.H.,Bai, H.,Martinez, E.J.,Jensen, J.L.,Rees, P.A.,Hajduczki, A.,Chang, W.C.,Choe, M.,Yan, L.,Sterling, S.L.,Swafford, I.,Kuklis, C.,Soman, S.,King, J.,Corbitt, C.,Zemil, M.,Peterson, C.E.,Mendez-Rivera, L.,Townsley, S.M.,Donofrio, G.C.,Lal, K.G.,Tran, U.,Green, E.C.,Smith, C.,de Val, N.,Laing, E.D.,Broder, C.C.,Currier, J.R.,Gromowski, G.D.,Wieczorek, L.,Rolland, M.,Paquin-Proulx, D.,van Dyk, D.,Britton, Z.,Rajan, S.,Loo, Y.M.,McTamney, P.M.,Esser, M.T.,Polonis, V.R.,Michael, N.L.,Krebs, S.J.,Modjarrad, K.,Joyce, M.G.
Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.
Structure, 32:131-, 2024

PubMed Abstract: Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies.

PubMed: 38157856
DOI: 10.1016/j.str.2023.11.015

Experimental method

X-RAY DIFFRACTION (3.5 Å)