6XEY

Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-4


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.25 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 2.4 of the entry. See complete history


Literature

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.

Liu, L.Wang, P.Nair, M.S.Yu, J.Rapp, M.Wang, Q.Luo, Y.Chan, J.F.Sahi, V.Figueroa, A.Guo, X.V.Cerutti, G.Bimela, J.Gorman, J.Zhou, T.Chen, Z.Yuen, K.Y.Kwong, P.D.Sodroski, J.G.Yin, M.T.Sheng, Z.Huang, Y.Shapiro, L.Ho, D.D.

(2020) Nature 584: 450-456

  • DOI: https://doi.org/10.1038/s41586-020-2571-7
  • Primary Citation of Related Structures:  
    6XEY

  • PubMed Abstract: 

    The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy 1,2 . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml -1 . Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.


  • Organizational Affiliation

    Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Spike glycoprotein
A, B, C
1,288Severe acute respiratory syndrome coronavirus 2Mutation(s): 5 
Gene Names: S2
UniProt
Find proteins for P0DTC2 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTC2 
Go to UniProtKB:  P0DTC2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTC2
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
2-4 Heavy ChainD [auth F],
F [auth H],
G [auth J]
122Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
2-4 Light ChainE [auth G],
H [auth K],
I [auth L]
110Homo sapiensMutation(s): 0 
UniProt
Find proteins for A0A5C2GJG2 (Homo sapiens)
Explore A0A5C2GJG2 
Go to UniProtKB:  A0A5C2GJG2
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UniProt GroupA0A5C2GJG2
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J [auth D],
L [auth I],
N,
R,
S,
J [auth D],
L [auth I],
N,
R,
S,
T,
U
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseK [auth E],
O,
P
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 6
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
M, Q
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G90333CG
GlyCosmos:  G90333CG
GlyGen:  G90333CG
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AA [auth A]
AB [auth C]
BA [auth A]
BB [auth C]
CA [auth A]
AA [auth A],
AB [auth C],
BA [auth A],
BB [auth C],
CA [auth A],
CB [auth C],
DA [auth A],
DB [auth C],
EA [auth A],
EB [auth C],
FA [auth A],
GA [auth A],
HA [auth B],
IA [auth B],
JA [auth B],
KA [auth B],
LA [auth B],
MA [auth B],
NA [auth B],
OA [auth B],
PA [auth B],
QA [auth B],
RA [auth B],
SA [auth B],
TA [auth C],
UA [auth C],
V [auth A],
VA [auth C],
W [auth A],
WA [auth C],
X [auth A],
XA [auth C],
Y [auth A],
YA [auth C],
Z [auth A],
ZA [auth C]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.25 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Other privateChinaJack Ma Foundation

Revision History  (Full details and data files)

  • Version 1.0: 2020-07-22
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2020-08-12
    Changes: Database references, Structure summary
  • Version 2.2: 2020-08-26
    Changes: Database references
  • Version 2.3: 2020-09-02
    Changes: Database references
  • Version 2.4: 2021-01-27
    Changes: Structure summary