7K8Q

Crystal structure of an anti-SARS-CoV-2 human neutralizing antibody Fab fragment, C121


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.

Barnes, C.O.Jette, C.A.Abernathy, M.E.Dam, K.A.Esswein, S.R.Gristick, H.B.Malyutin, A.G.Sharaf, N.G.Huey-Tubman, K.E.Lee, Y.E.Robbiani, D.F.Nussenzweig, M.C.West Jr., A.P.Bjorkman, P.J.

(2020) Nature 588: 682-687

  • DOI: https://doi.org/10.1038/s41586-020-2852-1
  • Primary Citation of Related Structures:  
    7K8M, 7K8N, 7K8O, 7K8P, 7K8Q, 7K8R, 7K8S, 7K8T, 7K8U, 7K8V, 7K8W, 7K8X, 7K8Y, 7K8Z, 7K90

  • PubMed Abstract: 

    The coronavirus disease 2019 (COVID-19) pandemic presents an urgent health crisis. Human neutralizing antibodies that target the host ACE2 receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein 1-5 show promise therapeutically and are being evaluated clinically 6-8 . Here, to identify the structural correlates of SARS-CoV-2 neutralization, we solved eight new structures of distinct COVID-19 human neutralizing antibodies 5 in complex with the SARS-CoV-2 spike trimer or RBD. Structural comparisons allowed us to classify the antibodies into categories: (1) neutralizing antibodies encoded by the VH3-53 gene segment with short CDRH3 loops that block ACE2 and bind only to 'up' RBDs; (2) ACE2-blocking neutralizing antibodies that bind both up and 'down' RBDs and can contact adjacent RBDs; (3) neutralizing antibodies that bind outside the ACE2 site and recognize both up and down RBDs; and (4) previously described antibodies that do not block ACE2 and bind only to up RBDs 9 . Class 2 contained four neutralizing antibodies with epitopes that bridged RBDs, including a VH3-53 antibody that used a long CDRH3 with a hydrophobic tip to bridge between adjacent down RBDs, thereby locking the spike into a closed conformation. Epitope and paratope mapping revealed few interactions with host-derived N-glycans and minor contributions of antibody somatic hypermutations to epitope contacts. Affinity measurements and mapping of naturally occurring and in vitro-selected spike mutants in 3D provided insight into the potential for SARS-CoV-2 to escape from antibodies elicited during infection or delivered therapeutically. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2.


  • Organizational Affiliation

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
C121 Fab Heavy ChainA [auth H]241Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C121 Fab Light ChainB [auth L]216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GOL
Query on GOL

Download Ideal Coordinates CCD File 
C [auth H]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.304α = 90
b = 71.304β = 90
c = 404.844γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
Blu-Icedata collection
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesP01-AI138938-S1
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesP50 AI150464-13

Revision History  (Full details and data files)

  • Version 1.0: 2020-10-21
    Type: Initial release
  • Version 1.1: 2020-10-28
    Changes: Structure summary
  • Version 1.2: 2021-01-13
    Changes: Database references
  • Version 1.3: 2023-10-18
    Changes: Data collection, Database references, Refinement description