Helix 69: A Multitasking RNA Motif as a Novel Drug Target

High-resolution structures have shown that helix 69 (H69) of the large ribosomal subunit can assume variable conformational states during translation. Solution studies on small model RNAs, isolated subunits, and complete ribosomes also revealed a variety of H69 conformations. Specific nucleotides of H69 that undergo changes in their relative orientations within the ribosome structure play important roles in both translation and ribosome rescue. Furthermore, the presence of multiple pseudouridines influences the global conformational states of H69, and these highly conserved modifications play a role in regulating the positioning of key functional residues. Helix 69 has recently been identified as a novel antibiotic target site. Small molecules such as aminoglycosides bind to specific conformational states of H69 in bacterial ribosomes and affect the translation process. A variety of techniques have been employed to study H69, ranging from chemical synthesis to X-ray crystallography, highlighting the importance of a detailed evaluation of the underlying principles of RNA conformational dynamics and drug targeting.