Ribosome (28S ribosomal RNA) (28S rRNA)

The ribosome, specifically the sarcin/ricin loop (SRL) of the 28S ribosomal RNA, is the primary intracellular target for Mistletoe lectin I (ML-I), also known as viscumin. ML-I is a type II ribosome-inactivating protein (RIP) derived from the European mistletoe (Viscum album) that consists of an enzymatic A-chain and a carbohydrate-binding B-chain. The B-chain facilitates entry into the cell by binding to surface galactose residues, after which the A-chain is released into the cytosol to enzymatically depurinate the 28S rRNA. This action permanently halts protein translation, making the ribosome a critical focal point for the cytotoxic effects of mistletoe-based therapies (PubMed: 11473357, Wikipedia: Viscumin). In clinical oncology, this mechanism is utilized through mistletoe extracts or recombinant viscumin (Aviscumine) to induce tumor cell death and stimulate host immune responses, particularly in European complementary medicine. However, because the ribosome is a fundamental component of all eukaryotic cells, the therapeutic use of ML-I requires precise administration to balance its anti-tumor activity against potential systemic toxicity and immunogenic reactions.

Other names

Sarcin/ricin loopSRLLarge ribosomal subunit60S ribosomal subunitRibosomal RNA N-glycosidase target

Mistletoe lectin I (ML-I) acts as a highly specific rRNA N-glycosidase that targets the sarcin/ricin loop (SRL) of the 28S ribosomal RNA. It catalyzes the depurination of a single adenine residue (A4324 in humans), which is essential for the binding of elongation factors EF-1 and EF-2. This modification irreversibly inactivates the ribosome, leading to the immediate cessation of protein synthesis and the subsequent activation of apoptotic pathways (PubMed: 15155613, UniProt: P06750).