Helix 69 of 23S ribosomal RNA (H69) (H69)

Helix 69 (H69) is a highly conserved 19-nucleotide hairpin loop located in Domain IV of the 23S ribosomal RNA (rRNA) within the large (50S) ribosomal subunit (Sumita et al., 2005, PubMed: 16155199). It plays a fundamental role in protein synthesis by forming the intersubunit bridge B2a, which is the most prominent contact point between the 50S and 30S subunits (Ali et al., 2006, PubMed: 16467448). H69 is involved in several stages of the translation cycle, including the selection of aminoacyl-tRNA, the translocation of tRNAs between ribosomal sites, and the recycling of the ribosome after peptide release (Dunkle et al., 2011, PubMed: 21525242). Due to its essential nature and high conservation across bacterial species, H69 serves as a significant target for various classes of antibiotics, such as aminoglycosides and tuberactinomycins (Jiang et al., 2014, PubMed: 24561505). These drugs bind to H69, often interfering with the conformational flexibility required for ribosome function or stabilizing the intersubunit bridge to prevent translocation. While H69 is a potent target for treating bacterial infections, the structural similarity between bacterial and human mitochondrial rRNA can lead to off-target effects, contributing to the toxicity profiles of drugs that interact with this region (Hobbie et al., 2008, PubMed: 18256154).

Other names

H6923S rRNA helix 69Domain IV helix 69Intersubunit bridge B2a

Antibiotics bind to H69 to stabilize the intersubunit bridge B2a, thereby inhibiting tRNA translocation and ribosome recycling (Jiang et al., 2014, PubMed: 24561505; Dunkle et al., 2011, PubMed: 21525242).