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Ribosomal 28S rRNA is a fundamental structural and functional component of the eukaryotic 60S ribosomal subunit, playing a central role in the translation of messenger RNA into proteins. A highly conserved region known as the sarcin/ricin loop (SRL) is critical for the interaction with elongation factors EF-1 and EF-2, which facilitate the translocation step of protein synthesis. Mistletoe lectin A-subunit (ML-A), a Type II ribosome-inactivating protein (RIP) found in Viscum album, specifically targets this loop. ML-A functions as an N-glycosidase that removes a single adenine residue (A4324 in humans) from the SRL, leading to the irreversible inactivation of the ribosome. This halt in protein synthesis triggers cellular stress responses and leads to apoptosis. In therapeutic applications, particularly in complementary oncology, mistletoe extracts and recombinant lectins like aviscumine are used to exploit this mechanism to induce cell death in malignant cells and stimulate the immune system.
The A-subunit of mistletoe lectin acts as a site-specific N-glycosidase that depurinates the adenine residue at position 4324 within the sarcin/ricin loop of the 28S rRNA, thereby preventing the binding of elongation factors and irreversibly inhibiting protein synthesis.
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