Helix 69 (H69) of 23S ribosomal RNA serves as a unique model system to study the impact of modified bases on RNA structure and function, and to screen potential antibiotics. H69 is located at the functionally important core domain of the bacterial ribosome, participates in key intersubunit bridge B2a interactions, and plays important roles in translation. This helix exists in multiple conformational states, and interacts with a number of translation factors at different stages of protein synthesis. Chemical probing analyses revealed that H69 undergoes structural rearrangements upon ribosome association, particularly at positions A1913 and A1918, with the various conformational states being influenced by solution conditions (e.g., concentration of Mg~(2+), pH value, and temperature) as well as pseudouridine (Ψ) modifications. Residue A1913 is proposed to be important for high-fidelity translation and efficient termination.Moreover, flexibility of the H69 stem region may help to accommodate the twisting energy from rotation of the subunits. Since H69 is a highly dynamic RNA domain, altering or regulating these important conformational states with small molecules could be a promising way to disrupt bacterial ribosome translation. Development of a method to easily monitor these changes is therefore important in order to understand H69 dynamics in solution, as well as to discover H69-targeting ligands.
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