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Title | Neutralizing antibody 5-7 defines a distinct site of vulnerability in SARS-CoV-2 spike N-terminal domain. |
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Journal, issue, pages | Cell Rep, Vol. 37, Issue 5, Page 109928, Year 2021 |
Publish date | Nov 2, 2021 |
Authors | Gabriele Cerutti / Yicheng Guo / Pengfei Wang / Manoj S Nair / Maple Wang / Yaoxing Huang / Jian Yu / Lihong Liu / Phinikoula S Katsamba / Fabiana Bahna / Eswar R Reddem / Peter D Kwong / David D Ho / Zizhang Sheng / Lawrence Shapiro / |
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 ...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. |
External links | Cell Rep / PubMed:34706271 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 Å |
Structure data | EMDB-24708, PDB-7rw2: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing antibody / Fusion protein / Spike glycoprotein / COVID-19 / N-terminal domain / NTD / 5-7 / VIRAL PROTEIN-IMMUNE SYSTEM complex |