Eukaryotic ribosome (80S ribosome) (80S ribosome)

The eukaryotic ribosome, frequently referred to as the host cell ribosome in the context of viral infection and toxicology, is a massive ribonucleoprotein complex responsible for all cytoplasmic protein synthesis (Nature, 2011). It consists of a small 40S subunit, which decodes mRNA, and a large 60S subunit, which catalyzes peptide bond formation via its peptidyl transferase center (Science, 2010). While many antibiotics target bacterial ribosomes, the host ribosome is the specific target of certain therapeutic agents like omacetaxine mepesuccinate, used to treat chronic myeloid leukemia by inhibiting the initial step of translation (Blood, 2012). It is also the target of potent ribosome-inactivating proteins (RIPs) such as ricin and Shiga toxin, which irreversibly damage the 28S rRNA to arrest protein synthesis (Journal of Biological Chemistry, 2001). Furthermore, the host ribosome is a critical site of conflict during viral infections, as viruses like SARS-CoV-2 employ specialized proteins to hijack or obstruct the machinery to prioritize viral protein production (Science, 2020). Due to its essential role in cell viability, the host ribosome represents a high-stakes target where therapeutic index and selectivity are paramount.

Other names

Host cell ribosomeCytoplasmic ribosome80S ribosome complexEukaryotic translation machinery

Inhibition of protein synthesis by binding to the A-site cleft of the peptidyl transferase center (PTC) to prevent aminoacyl-tRNA positioning, or through enzymatic depurination of the sarcin/ricin loop in the 28S rRNA which prevents elongation factor binding (PubMed, 2012; JBC, 2001).