6CR1

adalimumab EFab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.52 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.154 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

EFab domain substitution as a solution to the light-chain pairing problem of bispecific antibodies.

Cooke, H.A.Arndt, J.Quan, C.Shapiro, R.I.Wen, D.Foley, S.Vecchi, M.M.Preyer, M.

(2018) MAbs 10: 1248-1259

  • DOI: https://doi.org/10.1080/19420862.2018.1519631
  • Primary Citation of Related Structures:  
    6CR1

  • PubMed Abstract: 

    Bispecific antibody therapeutics can expand the functionality of a conventional monoclonal antibody drug because they can bind multiple antigens. However, their great potential is counterbalanced by the challenges faced in their production. The classic asymmetric bispecific containing an Fc requires the expression of four unique chains - two light chains and two heavy chains; each light chain must pair with its correct heavy chain, which then must heterodimerize to form the full bispecific. The light-chain pairing problem has several solutions, some of which require engineering and optimization for each bispecific pair. Here, we introduce a technology called EFab Domain Substitution, which replaces the Cε2 of IgE for one of the CL/CH1 domains into one arm of an asymmetric bispecific to encourage the correct pairing of the light chains. EFab Domain Substitution provides very robust correct pairing while maintaining antibody function and is effective for many variable domains. We report its effect on the biophysical properties of an antibody and the crystal structure of the EFab domain substituted into the adalimumab Fab (PDB ID 6CR1).


  • Organizational Affiliation

    a Department of Biotherapeutic and Medicinal Sciences , Biogen , Cambridge , MA , USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Light chain of adalimumab EFab (VL-IgE CH2)A [auth L]211Homo sapiensMutation(s): 0 
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Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of adalimumab EFab (VH-IgE CH2)B [auth H]231Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.52 Å
  • R-Value Free: 0.179 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.154 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 125.413α = 90
b = 195.846β = 90
c = 48.779γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Entry History 

Deposition Data

  • Released Date: 2018-09-26 
  • Deposition Author(s): Arndt, J.W.

Revision History  (Full details and data files)

  • Version 1.0: 2018-09-26
    Type: Initial release
  • Version 1.1: 2018-10-03
    Changes: Data collection, Database references
  • Version 1.2: 2018-11-28
    Changes: Data collection, Database references
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description