Bacterial 50S ribosomal subunit L11–23S rRNA interface (GAC interface)

The bacterial 50S ribosomal subunit L11–23S rRNA interface is a critical structural and functional component of the GTPase-associated center (GAC) within the prokaryotic ribosome [1.3.3, 1.3.5]. This interface is formed by the interaction of ribosomal protein L11 (uL11) with a highly conserved 58-nucleotide domain of the 23S rRNA, specifically helices H43 and H44 [1.2.1, 1.3.1]. Its primary biological role is to facilitate the binding and activation of essential translation factors, such as elongation factor G (EF-G) and elongation factor Tu (EF-Tu), which are necessary for protein synthesis [1.3.1, 1.3.3]. Specifically, the interface stimulates the ribosome-dependent GTPase activity of these factors, driving the translocation of mRNA and tRNAs [1.3.3, 1.3.5]. This site is the primary target for the thiopeptide class of antibiotics, including thiostrepton and micrococcin, which bind in a cleft between the L11 N-terminal domain and the rRNA [1.2.1, 1.3.1]. By binding here, these drugs stabilize a specific conformation of the ribosome that prevents the necessary transitions for factor turnover or stable factor binding, thereby halting bacterial translation [1.3.1, 1.3.5]. While highly effective in vitro, the clinical utility of drugs targeting this interface has been limited by poor solubility and pharmacokinetic challenges [1.3.1]. Consequently, it remains a significant focus for the development of next-generation antimicrobials designed to overcome these limitations [1.2.1, 1.4.4].

Other names

GTPase-associated centerGACL11-binding domainL11-23S rRNA complexThiopeptide binding site

Inhibition of translation elongation by preventing the stable binding and turnover of elongation factors (e.g., EF-G) on the ribosome [1.3.1, 1.3.3].