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TitlePotent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite.
Journal, issue, pagesCell Host Microbe, Vol. 29, Issue 5, Page 819-833.e7, Year 2021
Publish dateMay 12, 2021
AuthorsGabriele Cerutti / Yicheng Guo / Tongqing Zhou / Jason Gorman / Myungjin Lee / Micah Rapp / Eswar R Reddem / Jian Yu / Fabiana Bahna / Jude Bimela / Yaoxing Huang / Phinikoula S Katsamba / Lihong Liu / Manoj S Nair / Reda Rawi / Adam S Olia / Pengfei Wang / Baoshan Zhang / Gwo-Yu Chuang / David D Ho / Zizhang Sheng / Peter D Kwong / Lawrence Shapiro /
PubMed AbstractNumerous 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- ...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.
External linksCell Host Microbe / PubMed:33789084 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.97 - 4.47 Å
Structure data

23125

7l2d

EMDB-23125, PDB-7l2d:
Cryo-EM structure of NTD-directed neutralizing antibody 1-87 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.55 Å

23126

7l2e

EMDB-23126, PDB-7l2e:
Cryo-EM structure of NTD-directed neutralizing antibody 4-18 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 2.97 Å

23127

7l2f

EMDB-23127, PDB-7l2f:
Cryo-EM structure of NTD-directed neutralizing antibody 5-24 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-23150:
Cryo-EM map of NTD-directed neutralizing antibody 1-68 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-23151:
Cryo-EM map of NTD-directed neutralizing antibody 2-51 in complex with prefusion SARS-CoV-2 spike glycoprotein
Method: EM (single particle) / Resolution: 3.71 Å

23489

7lqv

EMDB-23489, PDB-7lqv:
Cryo-EM structure of NTD-directed neutralizing antibody 4-8 Fab in complex with SARS-CoV-2 S2P spike
Method: EM (single particle) / Resolution: 3.25 Å

23490

7lqw

EMDB-23490, PDB-7lqw:
Cryo-EM structure of NTD-directed neutralizing antibody 2-17 Fab in complex with SARS-CoV-2 S2P spike
Method: EM (single particle) / Resolution: 4.47 Å

PDB-7l2c:
Crystallographic structure of neutralizing antibody 2-51 in complex with SARS-CoV-2 spike N-terminal domain (NTD)
Method: X-RAY DIFFRACTION / Resolution: 3.65 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-CA:
Unknown entry

ChemComp-ACT:
ACETATE ION / Acetate

ChemComp-CAC:
CACODYLATE ION / Cacodylic acid

ChemComp-PGE:
TRIETHYLENE GLYCOL / Polyethylene glycol

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsIMMUNE SYSTEM/Viral Protein / COVID-19 / SARS-CoV-2 / Viral protein / Spike glycoprotein / N-terminal domain / NTD / Neutralizing antibody / 2-51 / Fab / IMMUNE SYSTEM / IMMUNE SYSTEM-Viral Protein complex / Viral protein/Immune system / Fusion protein / NTD-directed antibody / 1-87 / Viral protein-Immune system complex / 4-18 / 5-24 / COVID / COVID19 / SARS-CoV2 / prefusion / neutralizing

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