Molecular dynamics simulations demonstrate tRNA recognition mechanisms in T-box riboswitches, suggesting implications for gene regulation and antibiotic targeting.
Amino acid availability is crucial for protein synthesis. T-box riboswitches regulate amino acid levels in bacteria by sensing tRNA aminoacylation, ensuring precise control of the biosynthesis and transport pathways. We used coarse-grained molecular dynamics simulations to probe the mechanism of tRNA recognition by a translational T-box riboswitch using the iles T-box riboswitch as a model system. We showed that the T-box aptamer transitions between undocked, predocked, and docked states with Mg2+ concentration governing their relative abundance. In the undocked and predocked states, the freely moving stem I catches tRNA from the solution using the "fly casting" mechanism. The tRNA-bound stem I then docks to stem II in a specific orientation stabilized by noncanonical hydrogen bonds. This docking enables interaction with the discriminator domain to sense tRNA aminoacylation and regulate gene expression. As T-box riboswitches are key antibiotic targets, our proposed mechanism reveals critical druggable sites, and the results have broader implications for understanding RNA–RNA interactions in cellular regulation.
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Mondal et al. (2025) studied this question.
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