60S ribosomal subunit exit site (E-site) (60S E-site)

The 60S ribosomal subunit exit site (E-site) is a critical functional pocket within the large subunit of the eukaryotic ribosome that facilitates the release of deacylated tRNA during the elongation phase of protein synthesis (Alberts et al., 2014). As one of the three conserved tRNA binding sites, the E-site plays a vital role in maintaining the fidelity and progression of the translation machinery by coordinating with the A and P sites during the translocation of the mRNA-tRNA complex (Ben-Shem et al., 2011, Science). This site is the primary target for several potent inhibitors of eukaryotic translation, most notably the glutarimide antibiotics cycloheximide and lactimidomycin, which bind to the E-site and sterically block the movement of tRNA, thereby arresting protein production (Schneider-Poetsch et al., 2010, Nature Chemical Biology). While these inhibitors are invaluable tools in molecular biology for studying translation dynamics, their therapeutic application is limited by a lack of selectivity between human and other eukaryotic ribosomes, leading to significant systemic toxicity (Garreau de Loubresse et al., 2014, Nature). However, the E-site remains a subject of intense research for the development of selective antifungal and antiparasitic agents that can distinguish between host and pathogen ribosomal structures. Additionally, dysregulation of ribosomal function at the E-site is implicated in various ribosomopathies and certain types of cancer, where altered translation rates contribute to disease progression.

Other names

Ribosomal E-siteExit site of the large ribosomal subunitE-site of the 60S subunit80S ribosomal E-site

Inhibition of translation elongation by binding to the E-site and sterically hindering the release of deacylated tRNA or the translocation of the mRNA-tRNA complex (Schneider-Poetsch et al., 2010, Nature Chemical Biology).