7NAB

Crystal structure of human neutralizing mAb CV3-25 binding to SARS-CoV-2 S MPER peptide 1140-1165

Summary for 7NAB

• Entry DOI: 10.2210/pdb7nab/pdb
• Descriptor: CV3-25 Fab Heavy Chain, CV3-25 Fab Light Chain, Spike protein S2, ... (6 entities in total)
• Functional Keywords: human neutralizing mab, mper-targeting, sars-cov-2, spike, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 101894.91

Authors

Chen, Y.,Tolbert, W.D.,Pazgier, M. (deposition date: 2021-06-21, release date: 2021-12-08, Last modification date: 2024-11-13)

Primary citation

Li, W.,Chen, Y.,Prevost, J.,Ullah, I.,Lu, M.,Gong, S.Y.,Tauzin, A.,Gasser, R.,Vezina, D.,Anand, S.P.,Goyette, G.,Chaterjee, D.,Ding, S.,Tolbert, W.D.,Grunst, M.W.,Bo, Y.,Zhang, S.,Richard, J.,Zhou, F.,Huang, R.K.,Esser, L.,Zeher, A.,Cote, M.,Kumar, P.,Sodroski, J.,Xia, D.,Uchil, P.D.,Pazgier, M.,Finzi, A.,Mothes, W.
Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern.
Cell Rep, 38:110210-110210, 2022

PubMed Abstract: Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV3-25, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in the RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.

PubMed: 34971573
DOI: 10.1016/j.celrep.2021.110210

Experimental method

X-RAY DIFFRACTION (2.15 Å)