E-site of the 60S eukaryotic ribosomal subunit (60S E-site)

The E-site of the 60S eukaryotic ribosomal subunit is a critical functional domain within the large ribosomal subunit responsible for the release of deacylated tRNA during protein synthesis (Wilson & Doudna Cate, 2012). As one of the three primary tRNA binding sites (A, P, and E), the E-site facilitates the final stage of the translation elongation cycle by holding the tRNA after its amino acid has been added to the growing polypeptide chain (Garreau de Loubresse et al., 2014). This site is structurally complex, involving interactions between ribosomal RNA (rRNA) and various ribosomal proteins, and its proper functioning is essential for the translocation of the mRNA-tRNA complex. In clinical and research contexts, the 60S E-site is a significant pharmacological target; for instance, the antifungal agent Sordarin selectively inhibits fungal protein synthesis by stabilizing the interaction between elongation factor 2 (eEF2) and the E-site (Justice et al., 1998). Similarly, the laboratory tool cycloheximide exerts its inhibitory effects by binding directly to this site, preventing the release of tRNA and halting translation (Schneider-Poetsch et al., 2010). Understanding the E-site's architecture and dynamics is vital for developing selective inhibitors that can distinguish between fungal and human ribosomes, thereby addressing infectious diseases while minimizing host toxicity. Dysregulation of ribosomal function at this site is also implicated in various ribosomopathies and the hyper-proliferative state of cancer cells (Robert et al., 2009).

Other names

Ribosomal exit site60S exit siteE-site of the large ribosomal subunittRNA exit site

Inhibition of translation elongation by blocking deacylated tRNA release or stabilizing elongation factor binding to the exit site (Schneider-Poetsch et al., 2010; Justice et al., 1998).