4GG8

Immune Receptor

4GG8 の概要

• エントリーDOI: 10.2210/pdb4gg8/pdb
• 関連するPDBエントリー: 4GG6
• 関連するBIRD辞書のPRD_ID: PRD_900003
• 分子名称: T-CELL RECEPTOR, SP3.4 ALPHA CHAIN, T-CELL RECEPTOR, SP3.4 BETA CHAIN, beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: immune receptor, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 101880.48

構造登録者

Broughton, S.E.,Theodossis, A.,Petersen, J.,Reid, H.H.,Rossjohn, J. (登録日: 2012-08-06, 公開日: 2012-10-24, 最終更新日: 2024-11-20)

主引用文献

Broughton, S.E.,Petersen, J.,Theodossis, A.,Scally, S.W.,Loh, K.L.,Thompson, A.,van Bergen, J.,Kooy-Winkelaar, Y.,Henderson, K.N.,Beddoe, T.,Tye-Din, J.A.,Mannering, S.I.,Purcell, A.W.,McCluskey, J.,Anderson, R.P.,Koning, F.,Reid, H.H.,Rossjohn, J.
Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease.
Immunity, 37:611-621, 2012

PubMed Abstract: Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T cell-mediated disorder that is induced by dietary gluten. Although it is established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition event that triggers disease pathology. We show that biased TCR usage (TRBV9(∗)01) underpins the recognition of HLA-DQ8-α-I-gliadin. The structure of a prototypical TRBV9(∗)01-TCR-HLA-DQ8-α-I-gliadin complex shows that the TCR docks centrally above HLA-DQ8-α-I-gliadin, in which all complementarity-determining region-β (CDRβ) loops interact with the gliadin peptide. Mutagenesis at the TRBV9(∗)01-TCR-HLA-DQ8-α-I-gliadin interface provides an energetic basis for the Vβ bias. Moreover, CDR3 diversity accounts for TRBV9(∗)01(+) TCRs exhibiting differing reactivities toward the gliadin epitopes at various deamidation states. Accordingly, biased TCR usage is an important factor in the pathogenesis of DQ8-mediated celiac disease.

PubMed: 23063329
DOI: 10.1016/j.immuni.2012.07.013

実験手法

X-RAY DIFFRACTION (3.2 Å)