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1s9v

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{{STRUCTURE_1s9v| PDB=1s9v | SCENE= }}
{{STRUCTURE_1s9v| PDB=1s9v | SCENE= }}
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'''Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide'''
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===Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15020763}}
==About this Structure==
==About this Structure==
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[[Category: Hla-dq2]]
[[Category: Hla-dq2]]
[[Category: Immune system]]
[[Category: Immune system]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:27:55 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:01:33 2008''

Revision as of 11:01, 29 July 2008

Template:STRUCTURE 1s9v

Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide

Template:ABSTRACT PUBMED 15020763

About this Structure

1S9V is a Protein complex structure of sequences from Homo sapiens. 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

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