1s9v

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spinqualitylabelsall models 1s9v, resolution 2.22Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[146880], Celiac disease, susceptibility to OMIM:[604305], Creutzfeldt-Jakob disease, variant, resistance to OMIM:[604305], Multiple sclerosis, susceptibility to OMIM:[604305]

About this Structure

1S9V is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease., Kim CY, Quarsten H, Bergseng E, Khosla C, Sollid LM, Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4175-9. Epub 2004 Mar 12. PMID:15020763

Page seeded by OCA on Fri Feb 15 16:53:01 2008