1S9V

Crystal structure of HLA-DQ2 complexed with deamidated gliadin peptide

1S9V の概要

• エントリーDOI: 10.2210/pdb1s9v/pdb
• 分子名称: HLA class II histocompatibility antigen, DQ(3) alpha chain, HLA class II histocompatibility antigen, DQ(1) beta chain, alpha-I gliadin, ... (5 entities in total)
• 機能のキーワード: immune system, hla-dq2
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01909
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 92638.08

構造登録者

Kim, C.-Y.,Quarsten, H.,Bergseng, E.,Khosla, C.,Sollid, L.M. (登録日: 2004-02-05, 公開日: 2004-03-02, 最終更新日: 2024-10-16)

主引用文献

Kim, C.-Y.,Quarsten, H.,Bergseng, E.,Khosla, C.,Sollid, L.M.
Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease
Proc.Natl.Acad.Sci.USA, 101:4175-4179, 2004

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.

PubMed: 15020763
DOI: 10.1073/pnas.0306885101

実験手法

X-RAY DIFFRACTION (2.22 Å)