Bacterial 16S ribosomal RNA helix 44 (16S rRNA h44) (16S rRNA h44)

The bacterial 16S ribosomal RNA helix 44 (h44) is a critical structural and functional element of the 30S ribosomal subunit, forming the core of the decoding center at the A-site (Ogle et al., 2001). Its primary biological function is to facilitate the accurate selection of aminoacyl-tRNA by monitoring codon-anticodon base pairing through a conformational change involving the flipping of residues A1492 and A1493 (Vicens & Westhof, 2001). This site is the principal target for the aminoglycoside class of antibiotics, which bind to the h44 internal loop and stabilize the active conformation of the decoding center (Magnet & Blanchard, 2005). This interaction leads to significant misreading of the mRNA template, resulting in the production of aberrant, toxic proteins that compromise the bacterial cell envelope. Because of its essential role in bacterial viability, h44 is a major focus for treating severe infections caused by aerobic Gram-negative bacilli. However, therapeutic challenges arise from the structural similarity between bacterial h44 and the human mitochondrial 12S rRNA, which can lead to drug-induced hearing loss and other toxicities (Hobbie et al., 2008). Resistance to drugs targeting this site often emerges through enzymatic modification of the rRNA or the drugs themselves.

Other names

16S rRNA A-siteHelix 44 of the 30S ribosomal subunitBacterial decoding centerh44

Aminoglycoside antibiotics bind to the internal loop of helix 44 in the 16S rRNA, forcing the conserved residues A1492 and A1493 into an extrahelical position (Ogle et al., 2001). This conformational change mimics the state induced by correct codon-anticodon pairing, thereby decreasing the threshold for tRNA selection and leading to the incorporation of incorrect amino acids, known as mistranslation (Vicens & Westhof, 2001). The resulting mistranslated proteins can insert into the bacterial membrane, causing leakage and eventual cell death (Magnet & Blanchard, 2005).