Eukaryotic 80S ribosome (80S ribosome)

The eukaryotic 80S ribosome is a massive ribonucleoprotein complex that serves as the primary site of protein synthesis in the cytoplasm of eukaryotic cells (Khatter et al., 2015, Nature). It is composed of a small 40S subunit and a large 60S subunit, which together facilitate the translation of genetic information from mRNA into functional proteins (Anger et al., 2013, Nature). While historically avoided as a drug target due to potential host toxicity, the 80S ribosome is now targeted by specific therapeutics like Omacetaxine mepesuccinate (Homoharringtonine) for the treatment of chronic myeloid leukemia (CML), where it inhibits the elongation step of translation (Gandhi et al., 2014, Blood). Additionally, certain natural toxins like ricin and Shiga toxin exert their lethal effects by irreversibly inactivating the 28S rRNA component of the 80S ribosome (Grela et al., 2019, Molecules). Dysregulation of ribosomal biogenesis and function is a key driver in various cancers and genetic disorders known as ribosomopathies, such as Diamond-Blackfan anemia (Mills and Green, 2017, Science). Because the 80S ribosome is essential for all cellular life, drugs targeting it must be carefully designed to exploit specific vulnerabilities in diseased cells or pathogens to minimize systemic safety concerns (Myasnikov et al., 2016, Nature Communications).

Other names

Cytoplasmic ribosome80S nucleoprotein complexEukaryotic ribosome

Inhibition of protein synthesis through various mechanisms including blocking the aminoacyl-tRNA binding site (A-site), inhibiting peptidyl transferase activity, or preventing the translocation of the ribosome along the mRNA (Wilson, 2014, Nature Reviews Molecular Cell Biology).