Conformational Pathways of Translational T-box Riboswitch Governing tRNA Recognition for Gene Regulation

Area of Science:

• Molecular Biology
• Biophysics
• Structural Biology

Background:

• T-box riboswitches are essential genetic elements in bacteria.
• They regulate amino acid biosynthesis and transport pathways by sensing tRNA aminoacylation.
• Precise control of amino acid homeostasis is vital for bacterial survival and growth.

Purpose of the Study:

• To elucidate the molecular mechanism of tRNA recognition by T-box riboswitches.
• To investigate the role of Mg2+ in T-box riboswitch conformational dynamics.
• To identify potential druggable sites on T-box riboswitches as antibiotic targets.

Main Methods:

• Coarse-grained molecular dynamics (MD) simulations.
• Utilized the iles T-box riboswitch as a model system.
• Analyzed RNA-RNA interactions and conformational transitions.

Main Results:

• T-box aptamers transition between undocked, predocked, and docked states, influenced by Mg2+ concentration.
• Stem I employs a 'fly casting' mechanism to capture tRNA.
• tRNA binding to stem I facilitates docking to stem II via noncanonical hydrogen bonds, enabling aminoacylation sensing.

Conclusions:

• A detailed mechanism for T-box riboswitch-tRNA recognition has been proposed.
• The study identifies critical druggable sites on T-box riboswitches.
• Findings provide insights into RNA-RNA interactions and cellular regulation, with implications for antibiotic development.