5U17

Structure of human MR1-DA-6-FP in complex with human MAIT A-F7 TCR

Summary for 5U17

• Entry DOI: 10.2210/pdb5u17/pdb
• Related: 5U16 5U1R 5U2V 5U6Q
• Descriptor: Major histocompatibility complex class I-related gene protein, MAIT T-cell receptor alpha chain, MAIT T-cell receptor beta chain, ... (9 entities in total)
• Functional Keywords: t-cell receptor complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 188709.16

Authors

Keller, A.N.,Rossjohn, J. (deposition date: 2016-11-28, release date: 2017-02-08, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.15 Å)