26sk | pdb_000026sk
Crystal structure of MAIT A-F7 TCR-MR1-uric acid
Structural highlights
FunctionHMR1_HUMAN Has antigen presentation function. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (MAIT). MAIT cells are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent.[1] Publication Abstract from PubMedThe major histocompatibility complex class I-related molecule (MR1) is a non-classical antigen-presenting protein that presents a diverse array of microbial, synthetic and host-generated small metabolites to mucosal-associated invariant T (MAIT) cells and other MR1-restricted T (MR1T) cell populations. Recent studies showed that MR1 binds carbonyl-nucleobase adducts, resulting in the activation of some MR1T cell clones. However, whether endogenous canonical nucleobases and their derivatives can impact the MR1 axis remains unclear. Here, through biochemical and cellular screening of a library of canonical nucleobases and their catabolites, we demonstrate that the catabolites of purine degradation, namely uric acid, xanthine, and xanthosine, can, at high concentrations, bind MR1 and promote its intracellular retention, resulting in reduced MR1 surface expression. These purine-based nucleobases can compete with microbial and non-microbial ligands for MR1 binding. Analysis of three crystal structures of ligand-bound MR1 shows that these endogenous purine-based nucleobases adopt distinct modes of binding and interactions within the MR1 A'-pocket. Accordingly, we broaden the repertoire of MR1-ligandome by describing a group of host xanthine-based compounds that can bind MR1 and regulate its trafficking to the cell surface. The MHC-I related protein 1 MR1 can bind host purine catabolites.,Abdelaal MR, Lim XY, Mak JYW, Fairlie DP, McCluskey J, Corbett AJ, Gherardin NA, Awad W, Rossjohn J J Biol Chem. 2026 Aug 12;302(10):113428. doi: 10.1016/j.jbc.2026.113428. PMID:42586424[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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