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The eukaryotic 80S cytosolic ribosome is a massive ribonucleoprotein complex that serves as the primary site of protein synthesis in eukaryotic cells [Khatter et al., Nature, 2015]. Composed of a small 40S subunit and a large 60S subunit, it facilitates the translation of genetic information from messenger RNA (mRNA) into functional polypeptides [UniProt]. This process involves complex interactions between ribosomal RNA (rRNA), ribosomal proteins, transfer RNA (tRNA), and various translation factors. Beyond its fundamental role in cellular physiology, the 80S ribosome is implicated in several diseases; mutations in ribosomal proteins or assembly factors cause ribosomopathies like Diamond-Blackfan anemia [Narla & Ebert, Blood, 2010], and its upregulation is a hallmark of many cancers. While many antibiotics specifically target the bacterial 70S ribosome, the 80S ribosome is the target of potent toxins like ricin and therapeutic agents such as omacetaxine mepesuccinate, which is used to treat certain leukemias by inhibiting protein synthesis [Gandhi et al., 2014]. Understanding the 80S ribosome's structure and function is crucial for developing selective inhibitors that can distinguish between host and pathogen ribosomes or target the hyperactive translation machinery in malignant cells [Pelletier et al., Nature Reviews Drug Discovery, 2015].
Inhibition of translation initiation and elongation by binding to ribosomal subunits (e.g., the A-site) or enzymatically modifying ribosomal RNA (e.g., depurination of the sarcin/ricin loop) [Gandhi et al., 2014; Sandvig & van Deurs, 2002].
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