1S9V

Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.221 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease

Kim, C.-Y.Quarsten, H.Bergseng, E.Khosla, C.Sollid, L.M.

(2004) Proc Natl Acad Sci U S A 101: 4175-4179

  • DOI: https://doi.org/10.1073/pnas.0306885101
  • Primary Citation of Related Structures:  
    1S9V

  • PubMed Abstract: 

    Celiac disease, also known as celiac sprue, is a gluten-induced autoimmune-like disorder of the small intestine, which is strongly associated with HLA-DQ2. The structure of DQ2 complexed with an immunogenic epitope from gluten, QLQPFPQPELPY, has been determined to 2.2-A resolution by x-ray crystallography. The glutamate at P6, which is formed by tissue transglutaminase-catalyzed deamidation, is an important anchor residue as it participates in an extensive hydrogen-bonding network involving Lys-beta71 of DQ2. The gluten peptide-DQ2 complex retains critical hydrogen bonds between the MHC and the peptide backbone despite the presence of many proline residues in the peptide that are unable to participate in amide-mediated hydrogen bonds. Positioning of proline residues such that they do not interfere with backbone hydrogen bonding results in a reduction in the number of registers available for gluten peptides to bind to MHC class II molecules and presumably impairs the likelihood of establishing favorable side-chain interactions. The HLA association in celiac disease can be explained by a superior ability of DQ2 to bind the biased repertoire of proline-rich gluten peptides that have survived gastrointestinal digestion and that have been deamidated by tissue transglutaminase. Finally, surface-exposed proline residues in the proteolytically resistant ligand were replaced with functionalized analogs, thereby providing a starting point for the design of orally active agents for blocking gluten-induced toxicity.


  • Organizational Affiliation

    Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class II histocompatibility antigen, DQ(3) alpha chain
A, D
193Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01909 (Homo sapiens)
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Go to UniProtKB:  P01909
PHAROS:  P01909
GTEx:  ENSG00000196735 
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UniProt GroupP01909
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HLA class II histocompatibility antigen, DQ(1) beta chain
B, E
198Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01920 (Homo sapiens)
Explore P01920 
Go to UniProtKB:  P01920
PHAROS:  P01920
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UniProt GroupP01920
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
alpha-I gliadin
C, F
11N/AMutation(s): 0 
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.22 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.221 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.11α = 90
b = 93.75β = 90
c = 102.72γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-03-02
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance