7RW2

Cryo-EM structure of NTD-directed neutralizing antibody 5-7 in complex with prefusion SARS-CoV-2 spike glycoprotein

Replaces:  7N01

Summary for 7RW2

• Entry DOI: 10.2210/pdb7rw2/pdb
• EMDB information: 24708
• Descriptor: Spike glycoprotein, 5-7 heavy chain, 5-7 light chain, ... (5 entities in total)
• Functional Keywords: neutralizing antibody, fusion protein, spike glycoprotein, covid-19, n-terminal domain, ntd, 5-7, 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: 591078.99

Authors

Cerutti, G.,Shapiro, L. (deposition date: 2021-08-19, release date: 2021-09-01, Last modification date: 2022-11-30)

Primary citation

Cerutti, G.,Guo, Y.,Wang, P.,Nair, M.S.,Wang, M.,Huang, Y.,Yu, J.,Liu, L.,Katsamba, P.S.,Bahna, F.,Reddem, E.R.,Kwong, P.D.,Ho, D.D.,Sheng, Z.,Shapiro, L.
Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain.
Cell Rep, 37:109928-109928, 2021

PubMed Abstract: Antibodies that potently neutralize SARS-CoV-2 target mainly the receptor-binding domain or the N-terminal domain (NTD). Over a dozen potently neutralizing NTD-directed antibodies have been studied structurally, and all target a single antigenic supersite in NTD (site 1). Here, we report the cryo-EM structure of a potent NTD-directed neutralizing antibody 5-7, which recognizes a site distinct from other potently neutralizing antibodies, inserting a binding loop into an exposed hydrophobic pocket between the two sheets of the NTD β sandwich. Interestingly, this pocket was previously identified as the binding site for hydrophobic molecules, including heme metabolites, but we observe that their presence does not substantially impede 5-7 recognition. Mirroring its distinctive binding, antibody 5-7 retains neutralization potency with many variants of concern (VOCs). Overall, we reveal that a hydrophobic pocket in NTD proposed for immune evasion can be used by the immune system for recognition.

PubMed: 34706271
DOI: 10.1016/j.celrep.2021.109928

Experimental method

ELECTRON MICROSCOPY (3.5 Å)