4GRL

Crystal structure of a autoimmune TCR-MHC complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.86 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 

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This is version 1.1 of the entry. See complete history


Literature

Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop.

Sethi, D.K.Gordo, S.Schubert, D.A.Wucherpfennig, K.W.

(2013) Nat Commun 4: 2623-2623

  • DOI: https://doi.org/10.1038/ncomms3623
  • Primary Citation of Related Structures:  
    4GRL, 4MAY

  • PubMed Abstract: 

    Self-reactive CD4 T cells are thought to have a central role in the pathogenesis of many chronic inflammatory human diseases. Microbial peptides can activate self-reactive T cells, but the structural basis for such crossreactivity is not well understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we report the structural mechanism of TCR crossreactivity with two distinct peptides from human pathogens. The structures show that a single TCR residue (CDR3α F95) makes the majority of contacts with the self-peptide and both microbial peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide-MHC surface. Further, a neighbouring residue located on the same TCR loop (CDR3α E98) forms an energetically critical interaction with the MHC molecule. These data show how binding by a self-reactive TCR favors crossreactivity between self and microbial antigens.


  • Organizational Affiliation

    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MHC class II HLA-DQ-alpha chain183Homo sapiensMutation(s): 0 
Gene Names: alpha chainHLA-DQ1HLA-DQA1MHC CLASS II MOLECULE
UniProt
Find proteins for Q30066 (Homo sapiens)
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Go to UniProtKB:  Q30066
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UniProt GroupQ30066
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
MHC class II antigen200Homo sapiensMutation(s): 0 
Gene Names: beta chainHLA-DQ1HLA-DQB1MHC CLASS II MOLECULE
UniProt
Find proteins for Q67AJ6 (Homo sapiens)
Explore Q67AJ6 
Go to UniProtKB:  Q67AJ6
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UniProt GroupQ67AJ6
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
TCR Hy.1B11 alpha chain209Homo sapiensMutation(s): 0 
Gene Names: TCR Hy.1B11 alpha chain
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
TCR Hy.1B11 beta chain268Homo sapiensMutation(s): 0 
Gene Names: TCR Hy.1B11 beta chain
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth B]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.86 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.204 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.011α = 90
b = 125.583β = 90
c = 134.794γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
XDSdata reduction
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-06
    Type: Initial release
  • Version 1.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary