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 8QPR

SARS-CoV-2 S protein bound to human neutralising antibody UZGENT_G5


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Integrating artificial intelligence-based epitope prediction in a SARS-CoV-2 antibody discovery pipeline: caution is warranted.

Acar, D.D.Witkowski, W.Wejda, M.Wei, R.Desmet, T.Schepens, B.De Cae, S.Sedeyn, K.Eeckhaut, H.Fijalkowska, D.Roose, K.Vanmarcke, S.Poupon, A.Jochmans, D.Zhang, X.Abdelnabi, R.Foo, C.S.Weynand, B.Reiter, D.Callewaert, N.Remaut, H.Neyts, J.Saelens, X.Gerlo, S.Vandekerckhove, L.

(2024) EBioMedicine 100: 104960-104960

  • DOI: https://doi.org/10.1016/j.ebiom.2023.104960
  • Primary Citation of Related Structures:  
    8QPR, 8QQ0

  • PubMed Abstract: 

    SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes. Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs. Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner. Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection. Full list of funders is provided at the end of the manuscript.


  • Organizational Affiliation

    HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, Ghent 9000, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Spike glycoprotein,Fibritin1,288Severe acute respiratory syndrome coronavirus 2Tequatrovirus T4
This entity is chimeric
Mutation(s): 10 
Gene Names: S2wac
UniProt
Find proteins for P0DTC2 (Severe acute respiratory syndrome coronavirus 2)
Explore P0DTC2 
Go to UniProtKB:  P0DTC2
Find proteins for P10104 (Enterobacteria phage T4)
Explore P10104 
Go to UniProtKB:  P10104
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0DTC2P10104
Glycosylation
Glycosylation Sites: 5Go to GlyGen: P0DTC2-1
Sequence AnnotationsExpand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
IgG light chain - FABB [auth D]216Homo sapiensMutation(s): 0 
Gene Names: IgG
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence AnnotationsExpand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
IgG heavy chain - FABC [auth E]229Homo sapiensMutation(s): 0 
Gene Names: IgG
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Glycosylation
Glycosylation Sites: 1
Sequence AnnotationsExpand
  • 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-glucopyranoseD [auth a],
E [auth B],
F
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 5
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranoseG [auth c],
H [auth G],
I [auth e]
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G21290RB
GlyCosmos:  G21290RB
GlyGen:  G21290RB
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.80 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONcryoSPARC
MODEL REFINEMENTPHENIX1.18.2_3874:

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Other governmentBelgium--

Revision History  (Full details and data files)

  • Version 1.0: 2024-01-31
    Type: Initial release
  • Version 1.1: 2024-11-06
    Changes: Data collection, Structure summary