5VKK

Crystal structure of Fab fragment of anti-CD22 Epratuzumab


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Molecular basis of human CD22 function and therapeutic targeting.

Ereno-Orbea, J.Sicard, T.Cui, H.Mazhab-Jafari, M.T.Benlekbir, S.Guarne, A.Rubinstein, J.L.Julien, J.P.

(2017) Nat Commun 8: 764-764

  • DOI: https://doi.org/10.1038/s41467-017-00836-6
  • Primary Citation of Related Structures:  
    5VKJ, 5VKK, 5VKM, 5VL3

  • PubMed Abstract: 

    CD22 maintains a baseline level of B-cell inhibition to keep humoral immunity in check. As a B-cell-restricted antigen, CD22 is targeted in therapies against dysregulated B cells that cause autoimmune diseases and blood cancers. Here we report the crystal structure of human CD22 at 2.1 Å resolution, which reveals that specificity for α2-6 sialic acid ligands is dictated by a pre-formed β-hairpin as a unique mode of recognition across sialic acid-binding immunoglobulin-type lectins. The CD22 ectodomain adopts an extended conformation that facilitates concomitant CD22 nanocluster formation on B cells and binding to trans ligands to avert autoimmunity in mammals. We structurally delineate the CD22 site targeted by the therapeutic antibody epratuzumab at 3.1 Å resolution and determine a critical role for CD22 N-linked glycosylation in antibody engagement. Our studies provide molecular insights into mechanisms governing B-cell inhibition and valuable clues for the design of immune modulators in B-cell dysfunction.The B-cell-specific co-receptor CD22 is a therapeutic target for depleting dysregulated B cells. Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation.


  • Organizational Affiliation

    Program in Molecular Medicine, The Hospital for Sick Children Research Institute, Toronto, ON, Canada, M5G 0A4.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epratuzumab Fab Heavy ChainA [auth H],
C [auth A]
219Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
UniProt
Find proteins for Q6N089 (Homo sapiens)
Explore Q6N089 
Go to UniProtKB:  Q6N089
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6N089
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Epratuzumab Fab Light ChainB [auth L],
D [auth B]
219Mus musculusHomo sapiens
This entity is chimeric
Mutation(s): 0 
UniProt
Find proteins for Q8TCD0 (Homo sapiens)
Explore Q8TCD0 
Go to UniProtKB:  Q8TCD0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TCD0
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.712α = 71.81
b = 61.564β = 81.07
c = 65.285γ = 75.95
Software Package:
Software NamePurpose
PHENIXrefinement
XSCALEdata scaling
PDB_EXTRACTdata extraction
XDSdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)Canada111111
Canadian Institutes of Health Research (CIHR)CanadaPJT-148811
Canadian Institutes of Health Research (CIHR)CanadaBPF-144483

Revision History  (Full details and data files)

  • Version 1.0: 2017-10-04
    Type: Initial release
  • Version 1.1: 2017-10-11
    Changes: Database references, Source and taxonomy
  • Version 1.2: 2017-10-25
    Changes: Database references
  • Version 1.3: 2018-01-31
    Changes: Structure summary
  • Version 1.4: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.5: 2023-10-04
    Changes: Data collection, Database references, Refinement description