7L2F

Cryo-EM structure of NTD-directed neutralizing antibody 5-24 in complex with prefusion SARS-CoV-2 spike glycoprotein

Summary for 7L2F

• Entry DOI: 10.2210/pdb7l2f/pdb
• EMDB information: 23127
• Descriptor: Spike glycoprotein, 5-24 heavy chain, 5-24 light chain, ... (6 entities in total)
• Functional Keywords: neutralizing antibody, fusion protein, spike glycoprotein, covid-19, ntd, ntd-directed antibody, 5-24, viral protein, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 9
• Total formula weight: 590087.71

Authors

Cerutti, G.,Shapiro, L. (deposition date: 2020-12-16, release date: 2021-03-24, Last modification date: 2024-11-20)

Primary citation

Cerutti, G.,Guo, Y.,Zhou, T.,Gorman, J.,Lee, M.,Rapp, M.,Reddem, E.R.,Yu, J.,Bahna, F.,Bimela, J.,Huang, Y.,Katsamba, P.S.,Liu, L.,Nair, M.S.,Rawi, R.,Olia, A.S.,Wang, P.,Zhang, B.,Chuang, G.Y.,Ho, D.D.,Sheng, Z.,Kwong, P.D.,Shapiro, L.
Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.
Cell Host Microbe, 29:819-, 2021

PubMed Abstract: Numerous antibodies that neutralize SARS-CoV-2 have been identified, and these generally target either the receptor-binding domain (RBD) or the N-terminal domain (NTD) of the viral spike. While RBD-directed antibodies have been extensively studied, far less is known about NTD-directed antibodies. Here, we report cryo-EM and crystal structures for seven potent NTD-directed neutralizing antibodies in complex with spike or isolated NTD. These structures defined several antibody classes, with at least one observed in multiple convalescent donors. The structures revealed that all seven antibodies target a common surface, bordered by glycans N17, N74, N122, and N149. This site-formed primarily by a mobile β-hairpin and several flexible loops-was highly electropositive, located at the periphery of the spike, and the largest glycan-free surface of NTD facing away from the viral membrane. Thus, in contrast to neutralizing RBD-directed antibodies that recognize multiple non-overlapping epitopes, potent NTD-directed neutralizing antibodies appear to target a single supersite.

PubMed: 33789084
DOI: 10.1016/j.chom.2021.03.005

Experimental method

ELECTRON MICROSCOPY (3.9 Å)