6PUM

Structure of human MAIT A-F7 TCR in complex with human MR1-2'D-5-OP-RU

6PUM の概要

• エントリーDOI: 10.2210/pdb6pum/pdb
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, TCR alpha chain, ... (8 entities in total)
• 機能のキーワード: mait, mr1, metablite presentation, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 189373.22

構造登録者

Awad, W.,Keller, A.N.,Rossjohn, J. (登録日: 2019-07-18, 公開日: 2020-02-19, 最終更新日: 2024-10-23)

主引用文献

Awad, W.,Ler, G.J.M.,Xu, W.,Keller, A.N.,Mak, J.Y.W.,Lim, X.Y.,Liu, L.,Eckle, S.B.G.,Le Nours, J.,McCluskey, J.,Corbett, A.J.,Fairlie, D.P.,Rossjohn, J.
The molecular basis underpinning the potency and specificity of MAIT cell antigens.
Nat.Immunol., 21:400-411, 2020

PubMed Abstract: Mucosal-associated invariant T (MAIT) cells are activated by microbial riboflavin-based metabolite antigens when presented by MR1. How modifications to the potent antigen 5-OP-RU affect presentation by MR1 and MAIT cell activation remains unclear. Here we design 20 derivatives, termed altered metabolite ligands (AMLs), to dissect the impact of different antigen components on the human MAIT-MR1 axis. Analysis of 11 crystal structures of MAIT T cell antigen receptor (TCR)-MR1-AML ternary complexes, along with biochemical and functional assays, shows that MR1 cell-surface upregulation is influenced by ribityl and non-ribityl components of the ligand and the hydrophobicity of the MR1-AML interface. The polar ribityl chain of the AML strongly influences MAIT cell activation potency through dynamic compensatory interactions within a MAIT TCR-MR1-AML interaction triad. We define the basis by which the MAIT TCR can differentially recognize AMLs, thereby providing insight into MAIT cell antigen specificity and potency.

PubMed: 32123373
DOI: 10.1038/s41590-020-0616-6

実験手法

X-RAY DIFFRACTION (1.96 Å)