5U16

Structure of human MR1-2-OH-1-NA in complex with human MAIT A-F7 TCR

5U16 の概要

• エントリーDOI: 10.2210/pdb5u16/pdb
• 関連するPDBエントリー: 5U17 5U1R 5U2V 5U6Q 5U72
• 分子名称: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, MAIT T-cell receptor alpha chain, ... (9 entities in total)
• 機能のキーワード: t-cell receptor, 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: 188293.09

構造登録者

Keller, A.N.,Birkinshaw, R.W.,Rossjohn, J. (登録日: 2016-11-27, 公開日: 2017-02-15, 最終更新日: 2024-10-16)

主引用文献

Keller, A.N.,Eckle, S.B.,Xu, W.,Liu, L.,Hughes, V.A.,Mak, J.Y.,Meehan, B.S.,Pediongco, T.,Birkinshaw, R.W.,Chen, Z.,Wang, H.,D'Souza, C.,Kjer-Nielsen, L.,Gherardin, N.A.,Godfrey, D.I.,Kostenko, L.,Corbett, A.J.,Purcell, A.W.,Fairlie, D.P.,McCluskey, J.,Rossjohn, J.
Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.
Nat. Immunol., 18:402-411, 2017

PubMed Abstract: The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals.

PubMed: 28166217
DOI: 10.1038/ni.3679

実験手法

X-RAY DIFFRACTION (2 Å)