6DDM

Crystal Structure Analysis of the Epitope of an Anti-MICA Antibody


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.30 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

High-resolution glycosylation site-engineering method identifies MICA epitope critical for shedding inhibition activity of anti-MICA antibodies.

Lombana, T.N.Matsumoto, M.L.Berkley, A.M.Toy, E.Cook, R.Gan, Y.Du, C.Schnier, P.Sandoval, W.Ye, Z.Schartner, J.M.Kim, J.Spiess, C.

(2019) MAbs 11: 75-93

  • DOI: https://doi.org/10.1080/19420862.2018.1532767
  • Primary Citation of Related Structures:  
    6DDM, 6DDR, 6DDV

  • PubMed Abstract: 

    As an immune evasion strategy, MICA and MICB, the major histocompatibility complex class I homologs, are proteolytically cleaved from the surface of cancer cells leading to impairment of CD8 + T cell- and natural killer cell-mediated immune responses. Antibodies that inhibit MICA/B shedding from tumors have therapeutic potential, but the optimal epitopes are unknown. Therefore, we developed a high-resolution, high-throughput glycosylation-engineered epitope mapping (GEM) method, which utilizes site-specific insertion of N-linked glycans onto the antigen surface to mask local regions. We apply GEM to the discovery of epitopes important for shedding inhibition of MICA/B and validate the epitopes at the residue level by alanine scanning and X-ray crystallography (Protein Data Bank accession numbers 6DDM (1D5 Fab-MICA*008), 6DDR (13A9 Fab-MICA*008), 6DDV (6E1 Fab-MICA*008). Furthermore, we show that potent inhibition of MICA shedding can be achieved by antibodies that bind GEM epitopes adjacent to previously reported cleavage sites, and that these anti-MICA/B antibodies can prevent tumor growth in vivo.


  • Organizational Affiliation

    a Department of Antibody Engineering , Genentech Inc ., South San Francisco , USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Anti-MICA Fab fragment light chain clone 1D5215Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
MHC class I polypeptide-related sequence AB [auth C]94Homo sapiensMutation(s): 0 
Gene Names: MICAhCG_2001511
UniProt & NIH Common Fund Data Resources
Find proteins for Q96QC4 (Homo sapiens)
Explore Q96QC4 
Go to UniProtKB:  Q96QC4
GTEx:  ENSG00000204520 
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Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96QC4
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Anti-MICA Fab fragment heavy chain clone 1D5C [auth B]220Mus musculusMutation(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: 1.30 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.69α = 90
b = 50.177β = 90.85
c = 88.633γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-24
    Type: Initial release
  • Version 1.1: 2018-12-05
    Changes: Data collection, Database references
  • Version 1.2: 2019-01-23
    Changes: Data collection, Database references
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description